Pharmacogenetics of smoking cessation: role of nicotine target and metabolism genes.

paper Cited Public

Authors: Gold, Allison B; Lerman, Caryn
Year: 2012
Journal: Human genetics
PMID: 22290489
DOI: 10.1007/s00439-012-1143-9
PMCID: PMC3864572

#	Section	Preview
0	Introduction	Cigarette smoking continues to be the leading cause of preventable deaths in the United States,…
1	Introduction	FDA-approved approaches for smoking cessation include nicotine replacement therapy (NRT), bupropion,…
2	Introduction	and withdrawal, while reducing the reinforcing effects of nicotine from cigarette smoking (Rollema…
3	Introduction	Quitting smoking is very difficult due to nicotine’s addictive properties. There is substantial…
4	Introduction	Research has focused on identifying specific genetic influences on the ability to quit smoking. Such…
5	Neurobiology of nicotine — Nicotinic acetylcholine receptors	Neuronal nAChRs are heterogeneous cationic channels that are widely distributed in the nervous…
6	Neurobiology of nicotine — Nicotinic acetylcholine receptors	nAChRs are homopentameric or heteropentameric units that are localized primarily at presynaptic or…
7	Neurobiology of nicotine — Nicotinic acetylcholine receptors	nAChRs form a family of subtypes formed by five subunits (Gotti and Clementi 2004; Gotti et al.…
8	Neurobiology of nicotine — Neurotransmitter pathways and nicotine dependence	There is a well-supported role of nicotine as the pharmacological agent that maintains dependence.…
9	Neurobiology of nicotine — Neurotransmitter pathways and nicotine dependence	of the ventral tegmental area (VTA), resulting in dopamine release in the nucleus accumbens and…
10	Smoking cessation phenotypes	A well-defined phenotype is crucial to the success of genetics research. Smoking cessation, the…
11	Smoking cessation phenotypes	Nicotine dependence is associated with decreased rates of initial cessation and a higher risk of…
12	Smoking cessation phenotypes	Given the limited variability in successful quitting predicted by smoking behavior and nicotine…
13	Genetic research approaches	Nicotine dependence involves complex interactions between multiple genes and environmental factors…
14	Genetic research approaches	Efforts to discover chromosomal regions, and ultimately genes associated with a specific phenotype…
15	Genetic research approaches	11 chromosomes that have been identified in nicotine dependence linkage analyses, regions on…
16	Genetic research approaches	Candidate gene association studies investigate single nucleotide polymorphisms (SNPs) and other…
17	Genetic research approaches	Pathway-based association studies are a useful tool to study the associations of multiple genes…
18	Genetic research approaches	those important in nicotine addiction or smoking cessation, including gap junction, LTP, and MAPK…
19	Genetic research approaches	In contrast to candidate gene and pathway-based approaches, genome-wide association studies (GWAS)…

Name	Type
31,266 smokers GWAS local	cohort
3HC/cotinine local	phenotype
3-hydroxycotinine	drug
3′-hydroxycotinine local	drug
471 Caucasian smokers local	cohort
7-day point-prevalence local	phenotype
A529T local	variant
abstinence	phenotype
abstinence rates	phenotype
acetylcholine	drug
addiction	phenotype
adolescent animals	cohort
adolescent smoking	phenotype
adult rats	cohort
Adult treatment-seeking smokers local	cohort
affective signs of nicotine withdrawal local	phenotype
affective signs of withdrawal local	phenotype
affective symptoms	phenotype
Affective withdrawal signs local	phenotype
African American	cohort
African-American light smokers local	cohort
African-Americans	cohort
aging-induced cognitive impairments local	phenotype
alcohol	phenotype
anterior ventral tegmental area local	anatomy
Anterior VTA local	anatomy
antinociceptive effects local	phenotype
anxiety-like behavior	phenotype
anxiety-related behavior loss local	phenotype
Asian	cohort
attentional performance	phenotype
aversion	phenotype
aversion loss local	phenotype
aversive effects	phenotype
brain	anatomy
bupropion	drug
bupropion placebo-controlled randomized clinical trial local	cohort
C57BL/6J	cohort
Ca2+	drug
candidate gene study cohort local	cohort
case-control sample	cohort
Caucasians	cohort
Caucasian sample	cohort
cell body local	anatomy
central nervous system	anatomy
Cessation medication local	drug
cessation phenotypes local	phenotype
cessation treatment response local	phenotype
Chat	gene
cholinergic genes	gene
CHRNA10	gene
CHRNA2	gene
Chrna3	gene
Chrna4	gene
CHRNA4 A529T knock-in mice local	cohort
CHRNA4 Leu9'Ala local	variant
CHRNA4 Leu9Ser local	variant
CHRNA5	gene
CHRNA5-CHRNA3-CHRNB4 cluster	gene
CHRNA5-CHRNA3-CHRNB4 haplotype local	variant
CHRNA5_D398 local	variant
CHRNA5_D398N local	variant
CHRNA5 KO mice local	cohort
Chrna6	gene
Chrna7	gene
CHRNA8	gene
CHRNA9	gene
Chrnb2	gene
Chrnb3	gene
Chrnb4	gene
CHRNB4 African-American variant local	variant
CHRNB4 Caucasian variant local	variant
CHRNB4 knockout mice local	cohort
cigarettes	phenotype
clinical trials	cohort
CNS sensitivity to cholinergic stimulation local	phenotype
cocaine	phenotype
cognition	phenotype
cognitive flexibility	phenotype
cognitive signs of nicotine withdrawal local	phenotype
cognitive withdrawal symptoms local	phenotype
Cohort_291_EU local	cohort
Cohort_426_EU local	cohort
conditioned place aversion	phenotype
conditioned place preference	phenotype
Contextual cues local	phenotype
contextual fear conditioning deficits local	phenotype
continued use	phenotype
cotinine	drug
craving	phenotype
current smoking	phenotype
CYP2A6	gene
CYP2A6*1 local	variant
CYP2A61/1B local	variant
CYP2A6*1B local	variant
CYP2B6	gene
CYP2B6*4 allele local	variant
CYP2B6*6 haplotype local	variant
CYP2B6 K262R local	variant
CYP2B6 Q172H local	variant
DAT1 VNTR	variant
decreased likelihood of smoking cessation local	phenotype
dendrite	anatomy
Diminished nicotine sensitivity local	phenotype
discovery sample (472 European ancestry smokers) local	cohort
dopamine	drug
dopaminergic neurons	anatomy
DRD2	gene
DRD2-Taq1A local	variant
early smokers local	cohort
endogenous acetylcholine local	drug
enzyme	drug
epibatidine local	drug
European American smokers local	cohort
European ancestry	cohort
European women (2,474) local	cohort
extended transdermal nicotine therapy local	drug
Fagerström Test for Nicotine Dependence	phenotype
families	cohort
Family-based local	cohort
family-based non-treatment seekers local	cohort
faster nicotine and cotinine clearance local	phenotype
former smokers	phenotype
full sample	cohort
Galantamine local	drug
genetic factors	cohort
genetic variants	cohort
haplotypes	variant
Heavier smoking local	phenotype
heavy smoking	phenotype
higher 3-HC/cotinine ratios local	phenotype
High sensitivity α4* nAChRs response local	phenotype
hippocampus	anatomy
Hispanic	phenotype
Hoft et al. 2009 study local	cohort
human smokers local	cohort
hyperalgesia	phenotype
Hypothermic response to nicotine local	phenotype
inability to stop smoking local	phenotype
Increased anxiety local	phenotype
independent sample of smokers local	cohort
independent smoker cohort local	cohort
Inhaler local	drug
Initial abstinence local	phenotype
initial cessation local	phenotype
Initial sensitivity	phenotype
interpeduncular nucleus	anatomy
Jewish females local	cohort
K262R local	variant
Koreans	cohort
lapse local	phenotype
Lapse local	phenotype
large-scale genetic association cohort local	cohort
learning	phenotype
learning and memory deficits local	phenotype
Leu9Ser knock-in mice local	cohort
locus coeruleus	anatomy
long-term abstinence	phenotype
loss of control	phenotype
Lozenge local	drug
maternal smoking	phenotype
Maximal functional response to acetylcholine local	phenotype
mecamylamine	drug
medial habenula	anatomy
memory	phenotype
men	cohort
mesoaccumbens reward pathway local	anatomy
mesocorticolimbic dopaminergic pathways local	anatomy
methyllycaconitine	drug
mice	cohort
Na+	drug
nAChR subunit genes local	gene
nAChR subunits local	gene
neuronal excitability	phenotype
neuronal integration local	phenotype
neuronal nicotinic acetylcholine receptors local	gene
neurotransmitter release	phenotype
never smokers	phenotype
nicotine	drug
nicotine addiction	phenotype
nicotine clearance	phenotype
nicotine clearance rates local	phenotype
Nicotine cravings local	phenotype
nicotine dependence	phenotype
nicotine gum	drug
nicotine-induced seizures	phenotype
nicotine metabolism	phenotype
nicotine metabolism genes local	gene
nicotine metabolite ratio local	other
nicotine metabolite ratio	phenotype
nicotine metabolizing enzymes local	gene
nicotine nasal spray	drug
nicotine patch	drug
nicotine patch study local	cohort
Nicotine preference local	phenotype
nicotine replacement therapy	drug
nicotine reward	phenotype
nicotine sensitivity	phenotype
nicotine transdermal patch local	drug
nicotine use	phenotype
nicotine withdrawal	phenotype
nicotinic acetylcholine receptor	drug
Non-somatic signs of withdrawal local	phenotype
non-somatic withdrawal symptoms local	phenotype
normal activity allele local	phenotype
normal metabolizers local	phenotype
NRT	drug
NRTs local	drug
nucleus accumbens	anatomy
opioid	drug
other substances	phenotype
peripheral nervous system	anatomy
phenotype	phenotype
physical withdrawal symptoms local	phenotype
Plasma nicotine concentration local	phenotype
Poor motor learning local	phenotype
Positive motivational effects of nicotine local	phenotype
positive reinforcement	phenotype
posterior ventral tegmental area local	anatomy
presynaptic site local	anatomy
preterminal site local	anatomy
Preventable deaths local	phenotype
Psychosocial factors	phenotype
pVTA local	anatomy
pVTA dopaminergic neurons local	anatomy
pVTA dopaminergic neurons local	phenotype
Q172H local	variant
quit rate local	phenotype
quitting success	phenotype
race/ethnicity	phenotype
rats	cohort
Reduced antinociceptive effect local	phenotype
reduced CYP2A6 activity local	phenotype
reduced metabolizers local	phenotype
regular smoking	phenotype
Reinforcing properties of nicotine	phenotype
relapse	phenotype
response to bupropion local	phenotype
Response to bupropion treatment local	phenotype
response to nicotine therapy local	phenotype
Response to pharmaco-therapy local	phenotype
reward	phenotype
rewarding effects	phenotype
rs1044396	variant
rs1051730	variant
rs11072768 local	variant
rs12914008	variant
rs12914385	variant
rs12915366 local	variant
rs13280604 local	variant
rs1917810 local	variant
rs2072661	variant
rs2236196	variant
rs2304297 local	variant
rs3787138	variant
rs3811450 local	variant
rs4105144	variant
rs4262952 local	variant
rs4950 local	variant
rs518425 local	variant
rs6062899 local	variant
rs6090384 local	variant
rs6494212	variant
rs680244	variant
rs7004381 local	variant
rs8192475	variant
saline	drug
sensitivity to acute effects of smoking local	phenotype
sensitization	phenotype
severe inattention local	phenotype
slow metabolizer	phenotype
smokers treated with varenicline local	cohort
smoking	phenotype
smoking abstinence	phenotype
smoking behavior	phenotype
smoking cessation	phenotype
smoking cessation outcomes local	phenotype
smoking cessation therapies local	drug
smoking dependence	phenotype
smoking heaviness	phenotype
smoking initiation	phenotype
smoking persistence	phenotype
smoking phenotypes	phenotype
smoking relapse	phenotype
SNP	cohort
SNPs in CHRNA5-CHRNA3-CHRNB4 gene cluster local	variant
Somatic hyperalgesia local	phenotype
somatic signs local	phenotype
Somatic signs of withdrawal local	phenotype
somatic symptoms of nicotine withdrawal local	phenotype
somatic withdrawal symptoms local	phenotype
Somatic withdrawal symptoms local	phenotype
spatial working memory	phenotype
striatum	anatomy
subjective response to nicotine local	phenotype
Successful quitting	phenotype
T529A local	variant
Thorgeirsson and Stefansson sample (1,891 women) local	cohort
time to relapse	phenotype
tobacco use	phenotype
tolerance	phenotype
trace fear conditioning deficits local	phenotype
transdermal nicotine therapy local	drug
transdermal NRT	drug
transdermal patch	drug
treatment gains local	phenotype
treatment response	phenotype
treatment-seeking smokers	cohort
two independent trials local	cohort
United States	cohort
unsuccessful quit attempts local	phenotype
varenicline	drug
varenicline treatment cohort local	cohort
ventral striatum	anatomy
ventral tegmental area	anatomy
visuospatial attention local	phenotype
VTA	anatomy
wild-type mice	cohort
withdrawal	phenotype
withdrawal effects from drugs of abuse local	phenotype
withdrawal severity	phenotype
women	cohort
working memory	phenotype
α4 KO mice local	cohort
α4α6* nAChRs local	drug
α4β2* nAChRs local	drug
α6* nAChR local	gene
α7 agonists local	drug
α7 antagonists local	drug
α7 KO mice local	cohort
α7 nAChRs local	drug
αBgtx local	drug
α-conotoxin MII local	drug
α-conotoxin MII(H9A;L15A) local	drug
β2 KO mice local	cohort

Citation	PMID	DOI	Status
Alkondon, M et al., Neuropharmacology, 2000, Nicotine at concentrations found in cigarette smokers activates and desensitizes nicotinic acetylcholine receptors in CA1 interneurons of rat hippocampus	11044743	10.1016/s0028-3908(00)00156-8	Cited
Aubin, HJ et al., Thorax, 2008, Varenicline versus transdermal nicotine patch for smoking cessation: results from a randomised open-label trial	18263663	10.1136/thx.2007.090647	Cited
Audrain-McGovern, J et al., Pediatrics, 2007, The role of CYP2A6 in the emergence of nicotine dependence in adolescents	17130279	10.1542/peds.2006-1583	Cited
Bacciottini, L et al., Behav Brain Res, 2001, Interactions between histaminergic and cholinergic systems in learning and memory	11640972	10.1016/s0166-4328(01)00230-3	Cited
Baker, TB et al., Nicotine Tob Res, 2009, Human neuronal acetylcholine receptor A5-A3-B4 haplotypes are associated with multiple nicotine dependence phenotypes	19436041	10.1093/ntr/ntp064	Cited
Balfour, DJ, Nicotine Tob Res, 2004, The neurobiology of tobacco dependence: a preclinical perspective on the role of the dopamine projections to the nucleus accumbens [corrected]	15801566	10.1080/14622200412331324965	Cited
Benowitz, NL et al., Clin Pharmacol Ther, CYP2A6 genotype and the metabolism and disposition kinetics of nicotine	17112802	10.1016/j.clpt.2006.08.011	Cited
Benowitz, NL et al., Clin Pharmacol Ther, Female sex and oral contraceptive use accelerate nicotine metabolism	16678549	10.1016/j.clpt.2006.01.008	Cited
Benowitz, NL et al., Nicotine Tob Res, 2003, Nicotine metabolite ratio as a predictor of cigarette consumption	14577978	10.1080/1462220031000158717	Cited
Benowitz, NL et al., Prog Brain Res, 1989, Nicotine dependence and tolerance in man: pharmacokinetic and pharmacodynamic investigations	2587748	10.1016/s0079-6123(08)62487-5	Cited
Benowitz, NL, Clin Pharmacol Ther, 2008, Clinical pharmacology of nicotine: implications for understanding, preventing, and treating tobacco addiction	18305452	10.1038/clpt.2008.3	Cited
Beracochea, D et al., Psychopharmacology (Berl), 2008, Improvement of contextual memory by S 24795 in aged mice: comparison with memantine	18034231	10.1007/s00213-007-0987-5	Cited
Berrettini, W et al., Molecular Psychiatry, 2008, Alpha-5/alpha-3 nicotinic receptor subunit alleles increase risk for heavy smoking	18227835	10.1038/sj.mp.4002154	Cited
Besson, M et al., Psychopharmacology, 2006, Genetic dissociation of two behaviors associated with nicotine addiction: beta-2 containing nicotinic receptors are involved in nicotine reinforcement but not in withdrawal syndrome	16752141	10.1007/s00213-006-0418-z	Cited
Bierut, LJ et al., Am J Psychiatry, 2008, Variants in nicotinic receptors and risk for nicotine dependence	18519524	10.1176/appi.ajp.2008.07111711	Primary
Bierut, LJ et al., Hum Mol Genet, 2007, Novel genes identiWed in a high-density genome wide association study for nicotine dependence	17158188	10.1093/hmg/ddl441	Cited
Bitner, RS et al., J Neurosci, 2007, Broad-spectrum eYcacy across cognitive domains by alpha7 nicotinic acetylcholine receptor agonism correlates with activation of ERK1/2 and CREB phosphorylation pathways	17898229	10.1523/JNEUROSCI.2444-07.2007	Cited
Bloom, J et al., Pharmacogenet Genomics, 2011, The contribution of common CYP2A6 alleles to variation in nicotine metabolism among European-Americans	21597399	10.1097/FPC.0b013e328346e8c0	Cited
Boess, FG et al., J Pharmacol Exp Ther, 2007, The novel alpha7 nicotinic acetylcholine receptor agonist N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-[2-(methoxy)phenyl]-1-benzofuran-2-carboxamide improves working and recognition memory in rodents	17308038	10.1124/jpet.106.118976	Cited
Borrelli, B et al., Am J Prev Med, 2001, Smoking-cessation counseling in the home. Attitudes, beliefs, and behaviors of home healthcare nurses	11701297	10.1016/s0749-3797(01)00369-5	Cited
Breitling, LP et al., Biol Psychiatry, Smoking cessation and variations in nicotinic acetylcholine receptor subunits alpha-5, alpha-3, and beta-4 genes	18996504	10.1016/j.biopsych.2008.10.004	Cited
Breitling, LP et al., Pharmacogenomics J, Association of nicotinic acetylcholine receptor subunit alpha 4 polymorphisms with nicotine dependence in 5500 Germans	19290018	10.1038/tpj.2009.6	Cited
Brioni, JD et al., Adv Pharmacol, 1997, The pharmacology of (—)-nicotine and novel cholinergic channel modulators	8891102	10.1016/s1054-3589(08)60950-3	Cited
Brody, AL et al., Arch Gen Psychiatry, 2006, Cigarette smoking saturates brain alpha 4 beta 2 nicotinic acetylcholine receptors	16894067	10.1001/archpsyc.63.8.907	Cited
Bruijnzeel, AW et al., Neuropharmacology, 2004, Adaptations in cholinergic transmission in the ventral tegmental area associated with the aVective signs of nicotine withdrawal in rats	15380374	10.1016/j.neuropharm.2004.05.005	Cited
Butt, CM et al., Behav Neurosci, 2005, Modulation of nicotine but not ethanol preference by the mouse Chrna4 A529T polymorphism	15727510	10.1037/0735-7044.119.1.26	Cited
Cahill, K et al., Cochrane Database Syst Rev, 2011, Nicotine receptor partial agonists for smoking cessation	17253581	10.1002/14651858.CD006103.pub2	Cited
Caporaso, N et al., PloS One, 2009, Genome-wide and candidate gene association study of cigarette smoking behaviors	19247474	10.1371/journal.pone.0004653	Cited
Champtiaux, N et al., J Neurosci, 2002, Distribution and pharmacology of alpha 6-containing nicotinic acetylcholine receptors analyzed with mutant mice	11850448	10.1523/JNEUROSCI.22-04-01208.2002	Cited
Champtiaux, N et al., J Neurosci, 2003, Subunit composition of functional nicotinic receptors in dopaminergic neurons investigated with knock-out mice	12944511	10.1523/JNEUROSCI.23-21-07820.2003	Cited
Changeux, JP, Nature Rev Neurosci, 2010, Nicotine addiction and nicotinic receptors: lessons from genetically modified mice	20485364	10.1038/nrn2849	Cited
Cokkinides, VE et al., Am J Prev Med, 2005, Under-use of smoking-cessation treatments: results from the National Health Interview Survey, 2000	15626567	10.1016/j.amepre.2004.09.007	Cited
Conti, DV et al., Hum Mol Genet, 2008, Nicotinic acetylcholine receptor beta2 subunit gene implicated in a systems-based candidate gene study of smoking cessation	18593715	10.1093/hmg/ddn181	Cited
Corrigall, WA et al., Brain Res, 1994, Self-administered nicotine activates the mesolimbic dopamine system through the ventral tegmental area	7982062	10.1016/0006-8993(94)90401-4	Cited
Corrigall, WA et al., Psychopharmacology (Berl), 1992, The mesolimbic dopaminergic system is implicated in the reinforcing effects of nicotine	1615127	10.1007/BF02245149	Cited
Court, JA et al., Neuroscience, 1998, Dopamine and nicotinic receptor binding and the levels of dopamine and homovanillic acid in human brain related to tobacco use	9722142	10.1016/s0306-4522(98)00088-8	Cited
Damaj, MI et al., J Pharmacol Exp Ther, 2003, Characterization of spontaneous and precipitated nicotine withdrawal in the mouse	12970387	10.1124/jpet.103.054908	Cited
Dani, JA et al., Pharmacol Biochem Behav, 2001, Cellular mechanisms of nicotine addiction	11796143	10.1016/s0091-3057(01)00652-9	Cited
David, SP et al., Nicotine Tob Res, 2007, Pharmacogenetic clinical trial of sustained-release bupropion for smoking cessation	17654295	10.1080/14622200701382033	Cited
Davila-Garcia, MI et al., J Neurochem, 2003, Chronic nicotine administration does not increase nicotinic receptors labeled by [125I]epibatidine in adrenal gland, superior cervical ganglia, pineal or retina	12753083	10.1046/j.1471-4159.2003.01774.x	Cited
Davis, JA et al., Psychopharmacology, 2007, Beta2 subunit-containing nicotinic receptors mediate the enhancing effect of nicotine on trace cued fear conditioning in C57BL/6 mice	17136517	10.1007/s00213-006-0624-8	Cited
Dawkins, L et al., Addiction, 2009, Patterns of change in withdrawal symptoms, desire to smoke, reward motivation and response inhibition across 3 months of smoking abstinence	19344444	10.1111/j.1360-0443.2009.02522.x	Cited
Dempsey, D et al., Clin Pharmacol Ther, 2004, Nicotine metabolite ratio as an index of cytochrome P450 2A6 metabolic activity	15229465	10.1016/j.clpt.2004.02.011	Cited
Dicke, KE et al., Drug Metab Dispos, 2005, Nicotine and 4-(methylnit-rosamino)-1-(3-pyridyl)-butanone metabolism by cytochrome P450 2B6	16174803	10.1124/dmd.105.006718	Cited
Diehl, A et al., Int J Clin Pharmacol Ther, 2006, Galantamine reduces smoking in alcohol-dependent patients: a randomized, placebo-controlled trial	17190371	10.5414/cpp44614	Cited
Dizgah, IM et al., Neuroreport, 2005, Attenuation of morphine withdrawal signs by a D1 receptor agonist in the locus coeruleus of rats	16189477	10.1097/01.wnr.0000180142.91644.65	Cited
Drenan, RM et al., Neuron, 2008, In vivo activation of midbrain dopamine neurons via sensitized, high-affinity alpha 6 nicotinic acetylcholine receptors	18940593	10.1016/j.neuron.2008.09.009	Cited
Elbers, CC et al., Genet Epidemiol, 2009, Using genome-wide pathway analysis to unravel the etiology of complex diseases	19235186	10.1002/gepi.20395	Cited
Erlitzki, R et al., J Biol Chem, 2002, Multiple, conserved iron-responsive elements in the 3′-untranslated region of transferrin receptor mRNA enhance binding of iron regulatory protein 2	12200453	10.1074/jbc.M207918200	Cited
Etter, JF, Drug Alcohol Depend, 2005, A comparison of the content-, construct- and predictive validity of the cigarette dependence scale and the Fagerstrom test for nicotine dependence	15734226	10.1016/j.drugalcdep.2004.08.015	Cited
Fagerstrom, KO, Addict Behav, 1978, Measuring degree of physical dependence to tobacco smoking with reference to individualization of treatment	735910	10.1016/0306-4603(78)90024-2	Cited
Faucette, SR et al., Drug Metab Dispos, 2000, Validation of bupropion hydroxylation as a selective marker of human cytochrome P450 2B6 catalytic activity	10997944	—	Cited
Feng, Y et al., Am J Hum Genet, 2004, A common haplotype of the nicotine acetylcholine receptor alpha 4 subunit gene is associated with vulnerability to nicotine addiction in men	15154117	10.1086/422194	Cited
Fernandez-Salguero, P et al., Am J Hum Genet, 1995, A genetic polymorphism in coumarin 7-hydroxylation: sequence of the human CYP2A genes and identification of variant CYP2A6 alleles	7668294	—	Cited
Fidler, JA et al., Addiction, 2011, Strength of urges to smoke as a measure of severity of cigarette dependence: comparison with the Fagerstrom Test for Nicotine Dependence and its components	21134020	10.1111/j.1360-0443.2010.03226.x	Cited
Fiore, MC et al., US Department of Health and Human Services, 2008, Treating tobacco use and dependence: 2008 update. Clinical Practice Guideline	—	—	—
Flores, CM et al., J Neurochem, 1997, Differential regulation of neuronal nicotinic receptor binding sites following chronic nicotine administration	9349569	10.1046/j.1471-4159.1997.69052216.x	Cited
Flores, CM et al., Mol Pharmacol, 1992, A subtype of nicotinic cholinergic receptor in rat brain is composed of alpha 4 and beta 2 subunits and is up-regulated by chronic nicotine treatment	1732720	—	Cited
Fowler, CD et al., Nature, 2011, Habenular alpha5 nicotinic receptor subunit signalling controls nicotine intake	21278726	10.1038/nature09797	Cited
Freathy, RM et al., Hum Mol Genet, 2009, A common genetic variant in the 15q24 nicotinic acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) is associated with a reduced ability of women to quit smoking in pregnancy	19429911	10.1093/hmg/ddp216	Cited
Fujieda, M et al., Carcinogenesis, 2004, Evaluation of CYP2A6 genetic polymorphisms as determinants of smoking behavior and tobacco-related lung cancer risk in male Japanese smokers	15308589	10.1093/carcin/bgh258	Cited
Furberg, H et al., Genome Med, 2010, The public health utility of genome-wide association study results for smoking behavior	20423533	10.1186/gm147	Cited
Gaimarri, A et al., Brain Res Rev, 2007, Regulation of neuronal nicotinic receptor traffic and expression	17383007	10.1016/j.brainresrev.2007.02.005	Cited
Gerzanich, V et al., J Pharmacol Exp Ther, 1998, Alpha 5 subunit alters desensitization, pharmacology, Ca++ permeability and Ca++ modulation of human neuronal alpha 3 nicotinic receptors	9655874	—	Cited
Gonzales, D et al., JAMA, 2006, Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial	16820546	10.1001/jama.296.1.47	Cited
Goodz, SD et al., Methods Enzymol, 2002, Genotyping human CYP2A6 variants	12424898	10.1016/s0076-6879(02)57666-7	Cited
Gotti, C et al., Biochem Pharmacol, 2007, Heterogeneity and complexity of native brain nicotinic receptors	17597586	10.1016/j.bcp.2007.05.023	Cited
Gotti, C et al., Prog Neurobiol, 2004, Neuronal nicotinic receptors: from structure to pathology	15649582	10.1016/j.pneurobio.2004.09.006	Cited
Gotti, C et al., Trends Pharmacol Sci, 2006, Brain nicotinic acetylcholine receptors: native subtypes and their relevance	16876883	10.1016/j.tips.2006.07.004	Cited
Govind, AP et al., Biochem Pharmacol, 2009, Nicotine-induced upregulation of nicotinic receptors: underlying mechanisms and relevance to nicotine addiction	19540212	10.1016/j.bcp.2009.06.011	Cited
Grabus, SD et al., Psychopharmacology, 2005, Nicotine physical dependence and tolerance in the mouse following chronic oral administration	15365686	10.1007/s00213-004-2007-3	Cited
Greenbaum, L et al., Mol psychiatry, 2006, Why do young women smoke? I. Direct and interactive effects of environment, psychological characteristics and nicotinic cholinergic receptor genes	16314871	10.1038/sj.mp.4001774	Cited
Greenbaum, L et al., Mol Psychiatry, 2009, Differential contribution of genetic variation in multiple brain nicotinic cholinergic receptors to nicotine dependence: recent progress and emerging open questions	19564872	10.1038/mp.2009.59	Cited
Greenwood, PM et al., J Cogn Neurosci, 2005, Specificity of the effect of a nicotinic receptor polymorphism on individual differences in visuospatial attention	16269100	10.1162/089892905774597281	Cited
Gronier, B et al., Psychophar-macology, 2000, Activation of the mesocorticolimbic dopaminergic system by stimulation of muscarinic cholinergic receptors in the ventral tegmental area	10672627	10.1007/s002130050002	Cited
Gu, DF et al., Ann Hum Genet, 2000, The use of long PCR to confirm three common alleles at the CYP2A6 locus and the relationship between genotype and smoking habit	11281276	10.1046/j.1469-1809.2000.6450383.x	Cited
Hamidovic, A et al., Cancer Prev Res, 2011, Genetic variability of smoking persistence in African Americans	21436384	10.1158/1940-6207.CAPR-10-0362	Cited
Han, S et al., Am J Med Genet B Neuropsychiatr Genet, 2011, Association of CHRNA4 polymorphisms with smoking behavior in two populations	21445957	10.1002/ajmg.b.31177	Cited
Han, S et al., Biol Psychiatry, 2010, Meta-analysis of 15 genome-wide linkage scans of smoking behavior	19819424	10.1016/j.biopsych.2009.08.028	Cited
Heatherton, TF et al., Br J Addict, 1991, The Fagerstrom Test for Nicotine Dependence: a revision of the Fagerstrom Tolerance Questionnaire	1932883	10.1111/j.1360-0443.1991.tb01879.x	Cited
Heitjan, DF et al., Am J Med Genet Part B Neuropsychiatr Genet, 2008, Identification of pharmacogenetic markers in smoking cessation therapy	18165968	10.1002/ajmg.b.30669	Cited
Hentze, MW et al., Cell, 2004, Balancing acts: molecular control of mammalian iron metabolism	15109490	10.1016/s0092-8674(04)00343-5	Cited
Hernandez, CM et al., Neuroscience, 2005, Repeated nicotine exposure in rats: effects on memory function, cholinergic markers and nerve growth factor	15652996	10.1016/j.neuroscience.2004.10.006	Cited
Hernandez, LM et al., 2006, Genes, behavior, and the social environment: moving beyond the nature/nurture debate	20669442	—	Cited
Hesse, LM et al., Pharmacogenetics, 2004, Pharmacogenetic determinants of interindividual variability in bupropion hydroxylation by cytochrome P450 2B6 in human liver microsomes	15083067	10.1097/00008571-200404000-00002	Cited
Ho, MK et al., Clin Pharmacol Ther, 2009, Association of nicotine metabolite ratio and CYP2A6 genotype with smoking cessation treatment in African-American light smokers	19279561	10.1038/clpt.2009.19	Cited
Hoft, NR et al., Neuropsychopharmacology, 2009, Genetic association of the CHRNA6 and CHRNB3 genes with tobacco dependence in a nationally representative sample	18704094	10.1038/npp.2008.122	Cited
Hogg, RC et al., CNS Neurol Disord, 2004, Nicotinic acetylcholine receptors as drug targets. Current drug targets	15078187	10.2174/1568007043482507	Cited
Hogg, RC et al., Rev Physiol Biochem Pharmacol, 2003, Nicotinic acetylcholine receptors: from structure to brain function	12783266	10.1007/s10254-003-0005-1	Cited
Hoyle, E et al., Psychopharmacology (Berl), 2006, Impaired performance of alpha7 nicotinic receptor knockout mice in the five-choice serial reaction time task	17019565	10.1007/s00213-006-0549-2	Cited
Hughes, JR et al., Cochrane Database Syst Rev, 2007, Antidepressants for smoking cessation	17253443	10.1002/14651858.CD000031.pub3	Cited
Hughes, JR et al., Drug Alcohol Depend, 2010, A randomized, controlled trial of NRT-aided gradual vs. abrupt cessation in smokers actively trying to quit	20537810	10.1016/j.drugalcdep.2010.04.007	Cited
Hukkanen, J et al., Pharmacol Rev, 2005, Metabolism and disposition kinetics of nicotine	15734728	10.1124/pr.57.1.3	Cited
Hutchison, KE et al., Arch Gen Psychiatry, 2007, CHRNA4 and tobacco dependence: from gene regulation to treatment outcome	17768273	10.1001/archpsyc.64.9.1078	Cited
Iwahashi, K et al., Neuropsychobiology, 2004, Whole deletion of CYP2A6 gene (CYP2A6AST;4C) and smoking behavior	14981342	10.1159/000076418	Cited
Jackson, KJ et al., J Pharmacol Exp Ther, 2008, Differential role of nicotinic acetylcholine receptor subunits in physical and affective nicotine withdrawal signs	18184829	10.1124/jpet.107.132977	Cited
Jackson, KJ et al., J Pharmacol Exp Ther, 2009, The role of alpha6-containing nicotinic acetylcholine receptors in nicotine reward and withdrawal	19644040	10.1124/jpet.109.155457	Cited
Jaffrey, SR et al., Nucleic Acids Res, 1993, The interaction between the iron-responsive element binding protein and its cognate RNA is highly dependent upon both RNA sequence and structure	8233801	10.1093/nar/21.19.4627	Cited
Japuntich, SJ et al., Am J Prev Med, 2011, Smoker characteristics and smoking-cessation milestones	21335259	10.1016/j.amepre.2010.11.016	Cited
Johnstone, E et al., Clin Pharmacol Ther, 2006, Determinants of the rate of nicotine metabolism and effects on smoking behavior	17015050	10.1016/j.clpt.2006.06.011	Cited
Khiroug, SS et al., J Physiol, 2002, Rat nicotinic ACh receptor alpha7 and beta2 subunits co-assemble to form functional heteromeric nicotinic receptor channels	11956333	10.1113/jphysiol.2001.013847	Cited
King, DP et al., Neuropsychopharmacology, 2011, Smoking cessation pharmacogenetics: analysis of varenicline and bupropion in placebo-controlled clinical trials	22048466	10.1038/npp.2011.232	Cited
Klink, R et al., J Neurosci, 2001, Molecular and physiological diversity of nicotinic acetylcholine receptors in the midbrain dopaminergic nuclei	11222635	10.1523/JNEUROSCI.21-05-01452.2001	Cited
Koob, GF et al., Ciba Found Symp, 1993, The role of corticotropin-releasing factor in behavioural responses to stress	8491090	10.1002/9780470514368.ch14	Cited
Kubota, T et al., Phar-macogenomics J, 2006, CYP2A6 polymorphisms are associated with nicotine dependence and influence withdrawal symptoms in smoking cessation	16402086	10.1038/sj.tpj.6500348	Cited
Kuryatov, A et al., Mol Pharmacol, 2011, Acetylcholine receptor (AChR) alpha5 subunit variant associated with risk for nicotine dependence and lung cancer reduces (alpha4beta2)alpha5 AChR function	20881005	10.1124/mol.110.066357	Cited
Labarca, C et al., Proc Natl Acad Sci USA, 2001, Point mutant mice with hypersensitive alpha 4 nicotinic receptors show dopaminergic deficits and increased anxiety	11226318	10.1073/pnas.041582598	Cited
Lai, A et al., Mol Pharmacol, 2005, Long-term nicotine treatment decreases striatal alpha 6* nicotinic acetylcholine receptor sites and function in mice	15681595	10.1124/mol.104.006429	Cited
Lang, T et al., Pharmacogenetics, 2001, Extensive genetic polymorphism in the human CYP2B6 gene with impact on expression and function in human liver	11470993	10.1097/00008571-200107000-00004	Cited
Laviolette, SR et al., Nature Rev Neurosci, 2004, The neurobiology of nicotine addiction: bridging the gap from molecules to behaviour	14708004	10.1038/nrn1298	Cited
Laviolette, SR et al., Psychopharmacology (Berl), 2003, The motivational valence of nicotine in the rat ventral tegmental area is switched from rewarding to aversive following blockade of the alpha7-subunit-containing nicotinic acetylcholine receptor	12569428	10.1007/s00213-002-1317-6	Cited
Le Houezec, J, Int J Tuber Lung Dis, 2003, Role of nicotine pharmacokinetics in nicotine addiction and nicotine replacement therapy: a review	12971663	—	Cited
Learned-Coughlin, SM et al., Biol Psychiatry, 2003, In vivo activity of bupropion at the human dopamine transporter as measured by positron emission tomography	14550679	10.1016/s0006-3223(02)01834-6	Cited
Lee, AM et al., Biol Psychiatry, 2007, CYP2B6 genotype alters abstinence rates in a bupropion smoking cessation trial	17223085	10.1016/j.biopsych.2006.10.005	Cited
Lerman, C et al., Clin Pharmacol Ther, 2006, Nicotine metabolite ratio predicts efficacy of transdermal nicotine for smoking cessation	16765148	10.1016/j.clpt.2006.02.006	Cited
Lerman, C et al., Clin Pharmacol Ther, 2010, Genetic variation in nicotine metabolism predicts the efficacy of extended-duration transdermal nicotine therapy	20336063	10.1038/clpt.2010.3	Cited
Lerman, C et al., Pharmacogenetics, 2002, Pharmacogenetic investigation of smoking cessation treatment	12439223	10.1097/00008571-200211000-00007	Cited
Lessov, CN et al., Psychol Med, 2004, Defining nicotine dependence for genetic research: evidence from Australian twins	15500307	10.1017/s0033291703001582	Cited
Levi, M et al., J Pharmacokinet Pharmacodyn, 2007, Prediction methods for nicotine clearance using cotinine and 3-hydroxycotinine spot saliva samples II. Model application	17206525	10.1007/s10928-006-9026-0	Cited
Levin, ED et al., Behav Pharmacol, 1999, AR-R17779, and alpha7 nicotinic agonist, improves learning and memory in rats	10780509	10.1097/00008877-199911000-00014	Cited
Levin, ED et al., Brain Res Bull, 2003, Ventral hippocampal NMDA blockade and nicotinic effects on memory function	13679247	10.1016/s0361-9230(03)00183-7	Cited
Levin, ED, J Neurobiol, 2002, Nicotinic receptor subtypes and cognitive function	12436426	10.1002/neu.10151	Cited
Li, MD et al., Addiction, 2003, A meta-analysis of estimated genetic and environmental effects on smoking behavior in male and female adult twins	12492752	10.1046/j.1360-0443.2003.00295.x	Cited
Li, MD et al., Biol Psychiatry, 2008, Gene-gene interactions among CHRNA4, CHRNB2, BDNF, and NTRK2 in nicotine dependence	18534558	10.1016/j.biopsych.2008.04.026	Cited
Li, MD et al., Hum Mol Genet, 2005, Ethnic- and gender-speciWc association of the nicotinic acetylcholine receptor alpha4 subunit gene (CHRNA4) with nicotine dependence	15790597	10.1093/hmg/ddi132	Cited
Li, MD et al., PloS One, 2010, Associations of variants in CHRNA5/A3/B4 gene cluster with smoking behaviors in a Korean population	20808433	10.1371/journal.pone.0012183	Cited
Li, MD, Hum Genet, 2008, Identifying susceptibility loci for nicotine dependence: 2008 update based on recent genome-wide linkage analyses	18205015	10.1007/s00439-008-0473-0	Cited
Liang, Y et al., Neurogenetics, 2005, Functional polymorphisms in the human beta4 subunit of nicotinic acetylcholine receptors	15742216	10.1007/s10048-004-0199-7	Cited
Liu, JZ et al., Nat Genet, 2010, Meta-analysis and imputation refines the association of 15q25 with smoking quantity	20418889	10.1038/ng.572	Cited
Liu, YZ et al., Mol Psychiatry, 2009, Genome-wide association analyses suggested a novel mechanism for smoking behavior regulated by IL15	19188921	10.1038/mp.2009.3	Cited
Loboz, KK et al., Clin Pharmacol Ther, 2006, Cytochrome P450 2B6 activity as measured by bupropion hydroxylation: effect of induction by rifampin and ethnicity	16815319	10.1016/j.clpt.2006.03.010	Cited
Malaiyandi, V et al., Clin Pharmacol Ther, 2005, Implications of CYP2A6 genetic variation for smoking behaviors and nicotine dependence	15735609	10.1016/j.clpt.2004.10.011	Cited
Malaiyandi, V et al., Mol Psychiatry, 2006, Impact of CYP2A6 genotype on pretreatment smoking behaviour and nicotine levels from and usage of nicotine replacement therapy	16402128	10.1038/sj.mp.4001794	Cited
Malin, DH et al., Pharmacol Biochem Behav, 1998, Nicotine abstinence syndrome precipitated by the competitive nicotinic antagonist dihydro-beta-erythroidine	9678643	10.1016/s0091-3057(98)00028-8	Cited
Mansvelder, HD et al., J Neurobiol, 2002, Cellular and synaptic mechanisms of nicotine addiction	12436424	10.1002/neu.10148	Cited
Mansvelder, HD et al., Neuron, 2002, Synaptic mechanisms underlie nicotine-induced excitability of brain reward areas	11906697	10.1016/s0896-6273(02)00625-6	Cited
Mao, D et al., J Neurochem, 2008, The alpha4beta2alpha5 nicotinic cholinergic receptor in rat brain is resistant to up-regulation by nicotine in vivo	17961152	10.1111/j.1471-4159.2007.05011.x	Cited
Marchant, NL et al., Int J Neuropsychopharmacol, 2008, Prospective memory or prospective attention: physiological and pharmacological support for an attentional model	18042304	10.1017/S146114570700819X	Cited
Marighetto, A et al., Psychopharmacology (Berl), 2008, Comparative effects of the alpha7 nicotinic partial agonist, S 24795, and the cholinesterase inhibitor, donepezil, against aging-related deficits in declarative and working memory in mice	18265960	10.1007/s00213-007-1063-x	Cited
Markou, A et al., Neuropsychopharmacology, 1998, Neurobiological similarities in depression and drug dependence: a self-medication hypothesis	9471114	10.1016/S0893-133X(97)00113-9	Cited
Markou, A et al., Nicotine Tob Res, 2001, The nicotinic antagonist methyllycaconitine has differential effects on nicotine self-administration and nicotine withdrawal in the rat	11694204	10.1080/14622200110073380	Cited
Marks, JL et al., Addict Behav, 1999, Effects of menstrual phase on reactivity to nicotine	10189980	10.1016/s0306-4603(98)00033-1	Cited
Marks, MJ et al., Neuropharmacology, 2004, Subsets of acetylcholine-stimulated 86Rb+ efflux and [125I]-epibatidine binding sites in C57BL/6 mouse brain are differentially affected by chronic nicotine treatment	15111021	10.1016/j.neuropharm.2004.02.009	Cited
Marubio, LM et al., Nature, 1999, Reduced antinociception in mice lacking neuronal nicotinic receptor subunits	10235262	10.1038/19756	Cited
McCallum, SE et al., Psychopharmacology (Berl), 2006, Deletion of the beta 2 nicotinic acetylcholine receptor subunit alters development of tolerance to nicotine and eliminates receptor upregulation	16001112	10.1007/s00213-005-0076-6	Cited
Messina, ES et al., J Pharmacol Exp Ther, 1997, A major role for CYP2A6 in nicotine C-oxidation by human liver microsomes	9316878	—	Cited
Minematsu, N et al., Thorax, 2003, Association of CYP2A6 deletion polymorphism with smoking habit and development of pulmonary emphysema	12832682	10.1136/thorax.58.7.623	Cited
Mineur, YS et al., Biochem Pharmacol, 2008, Genetics of nicotinic acetylcholine receptors: relevance to nicotine addiction	17632086	10.1016/j.bcp.2007.06.010	Cited
Moore, D et al., BMJ, 2009, EVectiveness and safety of nicotine replacement therapy assisted reduction to stop smoking: systematic review and meta-analysis	19342408	10.1136/bmj.b1024	Cited
Morb Mortal Wkly Rep, 2010, Vital signs: current cigarette smoking among adults aged >18, 2009	20829747	—	Cited
Munafo, MR et al., Addiction, 2008, Genes and cigarette smoking	18190672	10.1111/j.1360-0443.2007.02071.x	Cited
Munafo, MR et al., Nicotine Tob Res, 2011, CHRNA3 rs1051730 Genotype and short-term smoking cessation	21690317	10.1093/ntr/ntr106	Cited
Mwenifumbo, JC et al., Drug Alcohol Depend, 2007, Nicotine metabolism and CYP2A6 activity in a population of black African descent: impact of gender and light smoking	17161559	10.1016/j.drugalcdep.2006.11.012	Cited
Mwenifumbo, JC et al., Hum Mutat, 2008, Novel and established CYP2A6 alleles impair in vivo nicotine metabolism in a population of Black African descent	18360915	10.1002/humu.20698	Cited
Mwenifumbo, JC et al., Pharmacogenomics, 2007, Genetic variability in CYP2A6 and the pharmacokinetics of nicotine	17979512	10.2217/14622416.8.10.1385	Cited
Nakajama, M et al., Clin Pharmacol Ther, 2006, Comprehensive evaluation of variability in nicotine metabolism and CYP2A6 polymorphic alleles in four ethnic populations	16952495	10.1016/j.clpt.2006.05.012	Cited
Nashmi, R et al., J Mol Neurosci, 2006, CNS localization of neuronal nicotinic receptors	17192671	10.1385/JMN:30:1:181	Cited
Nat Genet, 2010, Tobacco and Genetics Consortium. Genome-wide meta-analyses identify multiple loci associated with smoking behavior	20418890	10.1038/ng.571	Cited
Nestler, EJ, Nat Neurosci, 2005, Is there a common molecular pathway for addiction?	16251986	10.1038/nn1578	Cited
Nguyen, HN et al., J Pharmacol Exp Ther, 2003, Subtype-selective upregulation by chronic nicotine of high-affinity nicotinic receptors in rat brain demonstrated by receptor autoradiography	14560040	10.1124/jpet.103.056408	Cited
Nisell, M et al., Synapse, 1994, Systemic nicotine-induced dopamine release in the rat nucleus accumbens is regulated by nicotinic receptors in the ventral tegmental area	8134899	10.1002/syn.890160105	Cited
Palma, E et al., J Biol Chem, 1999, Nicotinic acetylcholine receptors assembled from the alpha7 and beta3 subunits	10373437	10.1074/jbc.274.26.18335	Cited
Papke, RL et al., J Pharmacol Exp Ther, 2001, Analysis of mecamylamine stereoisomers on human nicotinic receptor subtypes	11303054	—	Cited
Patterson, F et al., Clin Pharmacol Ther, 2008, Toward personalized therapy for smoking cessation: a randomized placebo-controlled trial of bupropion	18388868	10.1038/clpt.2008.57	Cited
Patterson, F et al., Drug Alcohol Depend, 2010, Working memory deficits predict short-term smoking resumption following brief abstinence	19733449	10.1016/j.drugalcdep.2009.07.020	Cited
Pergadia, ML et al., Psychol Med, 2006, Genetic analyses of DSM-IV nicotine withdrawal in adult twins	16749946	10.1017/S0033291706007495	Cited
Perkins, KA et al., Cancer Epidemiol Biomarkers Prev, 2009, Nicotinic acetylcholine receptor beta2 subunit (CHRNB2) gene and short-term ability to quit smoking in response to nicotine patch	19755656	10.1158/1055-9965.EPI-09-0166	Cited
Perry, DC et al., J Pharmacol Exp Ther, 2007, Chronic nicotine differentially regulates alpha6- and beta3-containing nicotinic cholinergic receptors in rat brain	17446303	10.1124/jpet.107.121228	Cited
Pianezza, ML et al., Nature, 1998, Nicotine metabolism defect reduces smoking	9655391	10.1038/31623	Cited
Picciotto, MR et al., J Neurosci, 2002, Neuronal systems underlying behaviors related to nicotine addiction: neural circuits and molecular genetics	11978809	10.1523/JNEUROSCI.22-09-03338.2002	Cited
Picciotto, MR et al., Nature, 1998, Acetylcholine receptors containing the beta2 subunit are involved in the reinforcing properties of nicotine	9428762	10.1038/34413	Cited
Piper, ME et al., J Consult Clin Psychol, 2004, A multiple motives approach to tobacco dependence: the Wisconsin Inventory of Smoking Dependence Motives (WISDM-68)	15065950	10.1037/0022-006X.72.2.139	Cited
Piper, ME et al., Nicotine Tob Res, 2006, Assessing tobacco dependence: a guide to measure evaluation and selection	16801292	10.1080/14622200600672765	Cited
Pomerleau, OF et al., Nicotine Tob Res, 2005, Nicotine dependence, depression, and gender: characterizing phenotypes based on withdrawal discomfort, response to smoking, and ability to abstain	15804681	10.1080/14622200412331328466	Cited
Pons, S et al., J Neurosci, 2008, Crucial role of alpha4 and alpha6 nicotinic acetylcholine receptor subunits from ventral tegmental area in systemic nicotine self-administration	19020025	10.1523/JNEUROSCI.3918-08.2008	Cited
Portugal, GS et al., Behav Brain Res, 2008, Genetic variability in nicotinic acetylcholine receptors and nicotine addiction: converging evidence from human and animal research	18571741	10.1016/j.bbr.2008.05.006	Cited
Portugal, GS et al., Neurobiol Learn Mem, 2008, Beta2 subunit containing acetylcholine receptors mediate nicotine withdrawal deficits in the acquisition of contextual fear conditioning	17584502	10.1016/j.nlm.2007.05.002	Cited
Ramirez-Latorre, J et al., Nature, 1996, Functional contributions of alpha5 subunit to neuronal acetylcholine receptor channels	8598930	10.1038/380347a0	Cited
Rao, Y et al., Mol Pharmacol, 2000, Duplications and defects in the CYP2A6 gene: identification, genotyping, and in vivo effects on smoking	10999944	10.1124/mol.58.4.747	Cited
Ray, R et al., J Neurogenet, 2009, Nicotine dependence pharmacogenetics: role of genetic variation in nicotine-metabolizing enzymes	19169923	10.1080/01677060802572887	Cited
Ray, R et al., Neuropsychopharmacology, 2010, Convergent evidence that choline acetyltransferase gene variation is associated with prospective smoking cessation and nicotine dependence	20147892	10.1038/npp.2010.7	Cited
Raybuck, JD et al., Eur J Neurosci, 2009, Nicotine withdrawal-induced deficits in trace fear conditioning in C57BL/6 mice—a role for high-affinity beta2 subunit-containing nicotinic acetylcholine receptors	19200240	10.1111/j.1460-9568.2008.06580.x	Cited
Rezvani, AH et al., Biol Psychiatry, 2001, Cognitive effects of nicotine	11230877	10.1016/s0006-3223(00)01094-5	Cited
Ring, HZ et al., Pharmacogenet Genomics, 2007, Gene-gene interactions between CYP2B6 and CYP2A6 in nicotine metabolism	18004205	10.1097/01.fpc.0000220560.59972.33	Cited
Risch, N et al., Science, 1996, The future of genetic studies of complex human diseases	8801636	10.1126/science.273.5281.1516	Cited
Roegge, CS et al., Animal models of cognitive impairment. Frontiers in neuroscience, 2006, Nicotine receptor antagonists in rats. Chap 3	—	—	—
Rogers, J et al., Ernst Schering Res Found Workshop, 2002, Elucidating molecular mechanisms of Alzheimer’s disease in microglial cultures	12066415	10.1007/978-3-662-05073-6_3	Cited
Rollema, H et al., Neuropharmacology, 2007, Pharmacological profile of the alpha4beta2 nicotinic acetylcholine receptor partial agonist varenicline, an effective smoking cessation aid	17157884	10.1016/j.neuropharm.2006.10.016	Cited
Rubinstein, ML et al., Pediatrics, 2008, Rate of nicotine metabolism and withdrawal symptoms in adolescent light smokers	18762498	10.1542/peds.2007-3679	Cited
Saccone, NL et al., Cancer Res, 2009, The CHRNA5-CHRNA3-CHRNB4 nicotinic receptor subunit gene cluster affects risk for nicotine dependence in African-Americans and in European-Americans	19706762	10.1158/0008-5472.CAN-09-0786	Cited
Saccone, SF et al., Hum Mol Genet, 2007, Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPs	17135278	10.1093/hmg/ddl438	Cited
Salas, R et al., J Neurosci Off J Soc Neurosci, 2009, Nicotinic receptors in the habenulo-interpeduncular system are necessary for nicotine withdrawal in mice	19279237	10.1523/JNEUROSCI.4934-08.2009	Cited
Salas, R et al., J Neurosci, 2003, Altered anxiety-related responses in mutant mice lacking the beta4 subunit of the nicotinic receptor	12867510	10.1523/JNEUROSCI.23-15-06255.2003	Cited
Salas, R et al., J Neurosci, Decreased signs of nicotine withdrawal in mice null for the beta4 nicotinic acetylcholine receptor subunit	15537871	10.1523/JNEUROSCI.1939-04.2004	Cited
Salas, R et al., Neuropharmacology, 2007, Decreased withdrawal symptoms but normal tolerance to nicotine in mice null for the alpha7 nicotinic acetylcholine receptor subunit	17920082	10.1016/j.neuropharm.2007.08.017	Cited
Salas, R et al., Neuropharmacology, The alpha3 and beta4 nicotinic acetylcholine receptor subunits are necessary for nicotine-induced seizures and hypolocomotion in mice	15275829	10.1016/j.neuropharm.2004.05.002	Cited
Salminen, O et al., Mol Pharmacol, 2004, Subunit composition and pharmacology of two classes of striatal presynaptic nicotinic acetylcholine receptors mediating dopamine release in mice	15155845	10.1124/mol.65.6.1526	Cited
Sarginson, JE et al., Am J Med Genet Part B Neuropsychiatric Genet, 2011, Markers in the 15q24 nicotinic receptor subunit gene cluster (CHRNA5-A3-B4) predict severity of nicotine addiction and response to smoking cessation therapy	21268243	10.1002/ajmg.b.31155	Cited
Schnoll, RA et al., Expert Opin Emerg Drugs, 2006, Current and emerging pharmacotherapies for treating tobacco dependence	16939383	10.1517/14728214.11.3.429	Cited
Schnoll, RA et al., Pharmacol Biochem Behav, 2009, Nicotine metabolic rate predicts successful smoking cessation with transdermal nicotine: a validation study	19000709	10.1016/j.pbb.2008.10.016	Cited
Schoedel, KA et al., Pharmaco-genetics, 2004, Ethnic variation in CYP2A6 and association of genetically slow nicotine metabolism and smoking in adult Caucasians	15475735	10.1097/00008571-200409000-00006	Cited
Shiffman, S et al., Addiction, 2006, Natural history of nicotine withdrawal	17156182	10.1111/j.1360-0443.2006.01635.x	Cited
Silagy, C et al., Cochrane Database Syst Rev, 2004, Nicotine replacement therapy for smoking cessation	15266423	10.1002/14651858.CD000146.pub2	Cited
Silagy, C et al., Online J Curr Clin Trials, 1994, The effectiveness of nicotine replacement therapies in smoking cessation	8305998	10.1016/0753-3322(94)90062-0	Cited
Slemmer, JE et al., J Pharmacol Exp Ther, 2000, Bupropion is a nicotinic antagonist	10991997	—	Cited
Slotkin, TA et al., Brain Res Bull, 2008, Adolescent nicotine treatment changes the response of acetylcholine systems to subsequent nicotine administration in adulthood	18395624	10.1016/j.brainresbull.2007.12.009	Cited
Smith, JW et al., Psychopharmacology (Berl), 2007, Ligands selective for alpha4beta2 but not alpha3beta4 or alpha7 nicotinic receptors generalise to the nicotine discriminative stimulus in the rat	17115136	10.1007/s00213-006-0596-8	Cited
Stead, LF et al., Cochrane Database Syst Rev, 2008, Nicotine replacement therapy for smoking cessation	18253970	10.1002/14651858.CD000146.pub3	Cited
Stitzel, JA et al., J Pharmacol Exp Ther, 2000, Potential role of the alpha4 and alpha6 nicotinic receptor subunits in regulating nicotine-induced seizures	10734154	—	Cited
Sullivan, PF et al., Arch Gen Psychiatry, 2001, Genetic case-control association studies in neuropsychiatry	11695947	10.1001/archpsyc.58.11.1015	Cited
Sullivan, PF et al., Nicotine Tob Res, 1999, The genetic epidemiology of smoking	11768187	10.1080/14622299050011811	Cited
Swan, GE et al., Pharmacogenet Genomics, 2005, Nicotine metabolism: the impact of CYP2A6 on estimates of additive genetic influence	15861035	10.1097/01213011-200502000-00007	Cited
Tapia, L et al., Mol Pharmacol, 2007, Ca2+ permeability of the (alpha4)3(beta2)2 stoichiometry greatly exceeds that of (alpha4)2(beta2)3 human acetylcholine receptors	17132685	10.1124/mol.106.030445	Cited
Tapper, AR et al., Science, 2004, Nicotine activation of alpha4* receptors: sufficient for reward, tolerance, and sensitization	15528443	10.1126/science.1099420	Cited
Terry, P et al., Psychopharmacology, 1997, Dopaminergic mediation of the discriminative stimulus effects of bupropion in rats	9399385	10.1007/s002130050443	Cited
Thorgeirsson, TE et al., Biol Psychiatry, 2008, Genetics of smoking behavior and its consequences: the role of nicotinic acetylcholine receptors	19000575	10.1016/j.biopsych.2008.09.010	Cited
Thorgeirsson, TE et al., Int J Epidemiol, 2010, Commentary: gene-environment interactions and smoking-related cancers	20123949	10.1093/ije/dyp385	Cited
Thorgeirsson, TE et al., Nat Genet, 2010, Sequence variants at CHRNB3-CHRNA6 and CYP2A6 aVect smoking behavior	20418888	10.1038/ng.573	Cited
Todd, RD et al., Mol Psychiatry, 2003, Mutational analysis of the nicotinic acetylcholine receptor alpha 4 subunit gene in attention deficit/hyperactivity disorder: evidence for association of an intronic polymorphism with attention problems	12556914	10.1038/sj.mp.4001257	Cited
Tritto, T et al., Nicotine Tob Res, 2004, Null mutant analysis of responses to nicotine: deletion of beta2 nicotinic acetylcholine receptor subunit but not alpha7 subunit reduces sensitivity to nicotine-induced locomotor depression and hypothermia	14982698	10.1080/14622200310001656966	Cited
Tritto, T et al., Pharmacogenetics, 2002, Variability in response to nicotine in the LSxSS RI strains: potential role of polymorphisms in alpha4 and alpha6 nicotinic receptor genes	11927835	10.1097/00008571-200204000-00004	Cited
Tucci, SA et al., Neurophar-macology, 2003, Methyllycaconitine (MLA) blocks the nicotine evoked anxiogenic effect and 5-HT release in the dorsal hippocampus: possible role of alpha7 receptors	12604094	10.1016/s0028-3908(02)00391-x	Cited
Tyndale, RF et al., Nicotine Tob Res, 1999, A common genetic defect in nicotine metabolism decreases risk for dependence and lowers cigarette consumption	11768189	10.1080/14622299050011831	Cited
Uhl, GR et al., BMC Genet, 2007, Molecular genetics of nicotine dependence and abstinence: whole genome association using 520,000 SNPs	17407593	10.1186/1471-2156-8-10	Cited
Vink, JM et al., Am J Hum Genet, 2009, Genome-wide association study of smoking initiation and current smoking	19268276	10.1016/j.ajhg.2009.02.001	Cited
Vink, JM et al., Behav Genet, 2005, Heritability of smoking initiation and nicotine dependence	15971021	10.1007/s10519-004-1327-8	Cited
Walters, CL et al., Psychopharmacology, 2006, The beta2 but not alpha7 subunit of the nicotinic acetylcholine receptor is required for nicotine-conditioned place preference in mice	16416156	10.1007/s00213-005-0295-x	Cited
Wang, F et al., J Biol Chem, 1996, Assembly of human neuronal nicotinic receptor alpha5 subunits with alpha3, beta2, and beta4 subunits	8663494	10.1074/jbc.271.30.17656	Cited
Wang, J et al., Alcohol Clin Exp Res, 2007, Regulation of platelet-derived growth factor signaling pathway by ethanol, nicotine, or both in mouse cortical neurons	17295719	10.1111/j.1530-0277.2006.00331.x	Cited
Wang, J et al., Neuropsychopharmacology, 2010, Common and unique biological pathways associated with smoking initiation/progression, nicotine dependence, and smoking cessation	19890259	10.1038/npp.2009.178	Cited
Wei, J et al., Hum Genet, 2010, Replication and extension of association of choline acetyltransferase with nicotine dependence in European and African American smokers	20383528	10.1007/s00439-010-0818-3	Cited
Whiting, P et al., J Neurosci Off J Soc Neurosci, 1986, Pharmacological properties of immuno-isolated neuronal nicotinic receptors	3531428	10.1523/JNEUROSCI.06-10-03061.1986	Cited
Whittaker, VP, Keio J Med, 1988, The organization of the cholinergic synapse	2904504	10.2302/kjm.37.234	Cited
Wilking, JA et al., Pharmacogenet Genomics, 2010, Chrna4 A529 knock-in mice exhibit altered nicotine sensitivity	20061993	10.1097/FPC.0b013e3283369347	Cited
Wu, J et al., J Physiol, Roles of nicotinic acetylcholine receptor beta subunits in function of human alpha4-containing nicotinic receptors	16825297	10.1113/jphysiol.2006.114645	Cited
Wu, P et al., BMC Publ Health, Effectiveness of smoking cessation therapies: a systematic review and meta-analysis	17156479	10.1186/1471-2458-6-300	Cited
Xian, H et al., Nicotine Tob Res, 2003, The heritability of failed smoking cessation and nicotine withdrawal in twins who smoked and attempted to quit	12745498	—	Cited
Xian, H et al., Psychol Med, 2005, Latent class typology of nicotine withdrawal: genetic contributions and association with failed smoking cessation and psychiatric disorders	15841876	10.1017/s0033291704003289	Cited
Xu, J et al., Nicotine Tob Res, 2008, Gender effects on mood and cigarette craving during early abstinence and resumption of smoking	18988078	10.1080/14622200802412929	Cited
Yamazaki, H et al., Arch Toxicol, 1999, Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes	10350185	10.1007/s002040050588	Cited
Yang, KC et al., Acta Pharmacol Sin, 2009, Mysterious alpha6-containing nAC-hRs: function, pharmacology, and pathophysiology	19498417	10.1038/aps.2009.63	Cited
Young, JW et al., Eur Neuropsychopharmacol, 2007, Impaired attention is central to the cognitive deficits observed in alpha 7 deficient mice	16650968	10.1016/j.euroneuro.2006.03.008	Cited
Zeiger, JS et al., Hum Mol Genet, 2008, The neuronal nicotinic receptor subunit genes (CHRNA6 and CHRNB3) are associated with subjective responses to tobacco	18055561	10.1093/hmg/ddm344	Cited
Zhang, H et al., Neuropsychopharmacology, 2010, Variation in the nicotinic acetylcholine receptor gene cluster CHRNA5-CHRNA3-CHRNB4 and its interaction with recent tobacco use influence cognitive flexibility	20631687	10.1038/npp.2010.95	Cited
Zhao-Shea, R et al., Neuropsychopharmacology, 2011, Nicotine-mediated activation of dopaminergic neurons in distinct regions of the ventral tegmental area	21289604	10.1038/npp.2010.240	Cited
Zoli, M et al., J, 2002, Identification of the nicotinic receptor subtypes expressed on dopaminergic terminals in the rat striatum	12388584	10.1523/JNEUROSCI.22-20-08785.2002	Cited

In this knowledge base

Title	Year	PMID
Genetic variation (CHRNA5), medication (combination nicotine replacement therapy vs. varenicline), and smoking cessation.	2015	26142345
Influence of a dopamine pathway additive genetic efficacy score on smoking cessation: results from two randomized clinical trials of bupropion.	2013	23941313

External

Title	Authors	Journal	Year	Link
Genomic medicine to reduce tobacco and related disorders: Translation to precision prevention and treatment.	Chen LS et al.	—	2023	→
How has the brain disease model of addiction contributed to tobacco control?	Hall W et al.	—	2023	→
Structure-activity relationships andz interindividual variability of drug responses: pharmacogenomics with antimicrobial drugs as a paradigm.	Thabet RH et al.	—	2023	→
Association of Polymorphism <i>CHRNA5</i> and <i>CHRNA3</i> Gene in People Addicted to Nicotine.	Chmielowiec K et al.	—	2022	→
Rodent models for nicotine withdrawal.	Chellian R et al.	—	2021	→
Korean male active smokers: quantifying their smoking habits and the transformation factor among biomarkers in urine and blood.	Yang J et al.	—	2020	→
The effect of genetic variations in the choline acetyltransferase gene (ChAT) on waterpipe tobacco smoking dependence.	Khabour OF et al.	—	2020	→
Chronic Obstructive Pulmonary Disease Risk and Smoking Cessation Changes Induced by <i>CHRNA5-A3</i> and <i>CHRNB3-A6</i> Variation in a Chinese Male Population.	Zhao L et al.	—	2019	→
Not all smokers appear to seek nicotine for the same reasons: implications for preclinical research in nicotine dependence.	Garcia-Rivas V et al.	—	2019	→
From genes to treatments: a systematic review of the pharmacogenetics in smoking cessation.	Salloum NC et al.	—	2018	→
Leveraging Genomic Data in Smoking Cessation Trials in the Era of Precision Medicine: Why and How.	Chen LS et al.	—	2018	→
Pathways to precision medicine in smoking cessation treatments.	Chen LS et al.	—	2018	→
Interaction between cytochrome P450 2A6 and Catechol-O-Methyltransferase genes and their association with smoking risk in young men.	Ou WC et al.	—	2017	→
Neuregulin signaling pathway in smoking behavior.	Gupta R et al.	—	2017	→
Prenatal fat exposure and hypothalamic PPAR β/δ: Possible relationship to increased neurogenesis of orexigenic peptide neurons.	Chang GQ et al.	—	2016	→
The Sociopharmacology of Tobacco Addiction: Implications for Understanding Health Disparities.	Leventhal AM	—	2016	→
What does addiction medicine expect from neuroscience? From genes and neurons to treatment responses.	Le Foll B	—	2016	→
An evolutionary medicine approach to understanding factors that contribute to chronic obstructive pulmonary disease.	Aoshiba K et al.	—	2015	→
Effect of genotype and methylation of CYP2D6 on smoking behaviour.	Tiili EM et al.	—	2015	→
Genetic variation (CHRNA5), medication (combination nicotine replacement therapy vs. varenicline), and smoking cessation.	Chen LS et al.	—	2015	→
Nicotine withdrawal.	McLaughlin I et al.	—	2015	→
Genetics and smoking.	Loukola A et al.	—	2014	→
Massive withdrawal symptoms and affective vulnerability are associated with variants of the CHRNA4 gene in a subgroup of smokers.	Lazary J et al.	—	2014	→
Plasma cotinine levels in cigarette smokers: impact of mental health and other correlates.	Bot M et al.	—	2014	→
Structure-function elucidation of a new α-conotoxin, Lo1a, from Conus longurionis.	Lebbe EK et al.	—	2014	→
Biomarkers for smoking cessation.	Bough KJ et al.	—	2013	→
Influence of a dopamine pathway additive genetic efficacy score on smoking cessation: results from two randomized clinical trials of bupropion.	David SP et al.	—	2013	→
Pharmacogenetic smoking cessation intervention in a health care setting: a pilot feasibility study.	McClure JB et al.	—	2013	→
Pharmacogenetics of chronic obstructive pulmonary disease.	Hizawa N	—	2013	→
Pharmacogenomics of drug-metabolizing enzymes: a recent update on clinical implications and endogenous effects.	Sim SC et al.	—	2013	→
The genetics of addiction.	Volkow ND et al.	—	2012	→