Interaction between the functional polymorphisms of the alcohol-metabolism genes in protection against alcoholism.
paper
Cited
Public
Unavailable
- Authors
- Chen, C C; Lu, R B; Chen, Y C; Wang, M F; Chang, Y C; Li, T K; Yin, S J
- Year
- 1999
- Journal
- American journal of human genetics
- PMID
- 10441588
- DOI
- 10.1086/302540
- PMCID
- PMC1377988
The genes that encode the major enzymes of alcohol metabolism, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), exhibit functional polymorphism. The variant alleles ADH2*2 and ADH3*1, which encode high-activity ADH isoforms, and the ALDH2*2 allele, which encodes the low-activity form of ALDH2, protect against alcoholism in East Asians. To investigate possible interactions among these protective genes, we genotyped 340 alcoholic and 545 control Han Chinese living in Taiwan at the ADH2, ADH3, and ALDH2 loci. After the influence of ALDH2*2 was controlled for, multiple logistic regression analysis indicated that allelic variation at ADH3 exerts no significant effect on the risk of alcoholism. This can be accounted for by linkage disequlibrium between ADH3*1 and ADH2*2 ALDH2*2 homozygosity, regardless of the ADH2 genotypes, was fully protective against alcoholism; no individual showing such homozygosity was found among the alcoholics. Logistic regression analyses of the remaining six combinatorial genotypes of the polymorphic ADH2 and ALDH2 loci indicated that individuals carrying one or two copies of ADH2*2 and a single copy of ALDH2*2 had the lowest risk (ORs 0.04-0.05) for alcoholism, as compared with the ADH2*1/*1 and ALDH2*1/*1 genotype. The disease risk associated with the ADH2*2/*2-ALDH2*1/*1 genotype appeared to be about half of that associated with the ADH2*1/*2-ALDH2*1/*1 genotype. The results suggest that protection afforded by the ADH2*2 allele may be independent of that afforded by ALDH2*2.
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| Coding and non-coding polymorphisms in alcohol dehydrogenase alters protein expression and alcohol-associated erythema. | Pershing LK et al. | β | 2008 | β |
| Ethnic related selection for an ADH Class I variant within East Asia. | Li H et al. | β | 2008 | β |
| Evidence for a two-stage model of dependence using the NESARC and its implications for genetic association studies. | Heiman GA et al. | β | 2008 | β |
| Explanatory models for psychiatric illness. | Kendler KS | β | 2008 | β |
| Gene therapy reduces ethanol intake in an animal model of alcohol dependence. | Ocaranza P et al. | β | 2008 | β |
| "Higher order" addiction molecular genetics: convergent data from genome-wide association in humans and mice. | Uhl GR et al. | β | 2008 | β |
| Major genetic components underlying alcoholism in Korean population. | Kim DJ et al. | β | 2008 | β |
| Molecular genetics of addiction and related heritable phenotypes: genome-wide association approaches identify "connectivity constellation" and drug target genes with pleiotropic effects. | Uhl GR et al. | β | 2008 | β |
| Molecular genetics of alcohol dependence and related endophenotypes. | Strat YL et al. | β | 2008 | β |
| Prevalence of self-reported hypersensitivity symptoms following intake of alcoholic drinks. | Linneberg A et al. | β | 2008 | β |
| Tolerance to disulfiram induced by chronic alcohol intake in the rat. | Tampier L et al. | β | 2008 | β |
| Underage drinking: a developmental framework. | Masten AS et al. | β | 2008 | β |
| Alcohol dehydrogenase 1B genotype and fetal alcohol syndrome: a HuGE minireview. | Green RF et al. | β | 2007 | β |
| Association of haplotypic variants in DRD2, ANKK1, TTC12 and NCAM1 to alcohol dependence in independent case control and family samples. | Yang BZ et al. | β | 2007 | β |
| Association of the ADHIB*3 allele with alcohol-related phenotypes in Trinidad. | Ehlers CL et al. | β | 2007 | β |
| Bayesian analysis of structural equation models with multinomial variables and an application to type 2 diabetic nephropathy. | Song XY et al. | β | 2007 | β |
| Contribution of the alcohol dehydrogenase-1B genotype and oral microorganisms to high salivary acetaldehyde concentrations in Japanese alcoholic men. | Yokoyama A et al. | β | 2007 | β |
| Effect of ADH1B genotype on alcohol consumption in young Israeli Jews. | Spivak B et al. | β | 2007 | β |
| Ethanol-responsive genes: identification of transcription factors and their role in metabolomics. | Uddin RK et al. | β | 2007 | β |
| Evidence of positive selection on a class I ADH locus. | Han Y et al. | β | 2007 | β |
| Gene-alcohol interactions in the metabolic syndrome. | Corella D | β | 2007 | β |
| Genetic variation and shared biological susceptibility underlying comorbidity in neuropsychiatry. | Palomo T et al. | β | 2007 | β |
| How gene-stress-behavior interactions can promote adolescent alcohol use: the roles of predrinking allostatic load and childhood behavior disorders. | Zimmermann US et al. | β | 2007 | β |
| Impact of the alcohol-dehydrogenase (ADH) 1C and ADH1B polymorphisms on drinking behavior in nonalcoholic Japanese. | Matsuo K et al. | β | 2007 | β |
| Joint effect of alcohol and usual sleep duration on the risk of dysglycemia. | Kadono M et al. | β | 2007 | β |
| Pharmacogenetic aspects of addictive behaviors. | Hejazi NS | β | 2007 | β |
| Pharmacokinetic and pharmacodynamic basis for partial protection against alcoholism in Asians, heterozygous for the variant ALDH2*2 gene allele. | Peng GS et al. | β | 2007 | β |
| Possible interaction between MAOA and DRD2 genes associated with antisocial alcoholism among Han Chinese men in Taiwan. | Wang TJ et al. | β | 2007 | β |
| Single nucleotide polymorphisms in alcohol dehydrogenase genes among some Indian populations. | Rao VR et al. | β | 2007 | β |
| Single nucleotide polymorphisms of the ALDH2 gene in six Indian populations. | Bhaskar LV et al. | β | 2007 | β |
| The genetics of alcohol metabolism: role of alcohol dehydrogenase and aldehyde dehydrogenase variants. | Edenberg HJ | β | 2007 | β |
| The polymorphism in acetaldehyde dehydrogenase 2 gene, causing a substitution of Glu > Lys(504), is not associated with coronary atherosclerosis severity in Han Chinese. | Xu F et al. | β | 2007 | β |
| Alcohol use among entrants to a Hong Kong University. | Griffiths S et al. | β | 2006 | β |
| A map of recent positive selection in the human genome. | Voight BF et al. | β | 2006 | β |
| A rational approach to the pharmacotherapy of alcohol dependence. | Petrakis IL | β | 2006 | β |
| Associations of variations in alcohol dehydrogenase genes with the level of response to alcohol in non-Asians. | Duranceaux NC et al. | β | 2006 | β |
| Clinical and genetic characteristics of Korean male alcoholics with and without attention deficit hyperactivity disorder. | Kim JW et al. | β | 2006 | β |
| Diplotype trend regression analysis of the ADH gene cluster and the ALDH2 gene: multiple significant associations with alcohol dependence. | Luo X et al. | β | 2006 | β |
| Distant HNF1 site as a master control for the human class I alcohol dehydrogenase gene expression. | Su JS et al. | β | 2006 | β |
| Do alcohol-metabolizing enzyme gene polymorphisms increase the risk of alcoholism and alcoholic liver disease? | Zintzaras E et al. | β | 2006 | β |
| Effects of variation at the ALDH2 locus on alcohol metabolism, sensitivity, consumption, and dependence in Europeans. | Dickson PA et al. | β | 2006 | β |
| Functional assessment of human alcohol dehydrogenase family in ethanol metabolism: significance of first-pass metabolism. | Lee SL et al. | β | 2006 | β |
| Genetic polymorphisms of alcohol and aldehyde dehydrogenase, dopamine and serotonin transporters in familial and non-familial alcoholism. | Choi IG et al. | β | 2006 | β |
| Identification of susceptibility loci for alcohol-related traits in the Irish Affected Sib Pair Study of Alcohol Dependence. | Kuo PH et al. | β | 2006 | β |
| Immunochemical features in the classification of human alcohol dehydrogenase family. | Lee SP et al. | β | 2006 | β |
| Meta-analyses of ALDH2 and ADH1B with alcohol dependence in Asians. | Luczak SE et al. | β | 2006 | β |
| The genetics of alcoholism: identifying specific genes through family studies. | Edenberg HJ et al. | β | 2006 | β |
| The UChA and UChB rat lines: metabolic and genetic differences influencing ethanol intake. | Quintanilla ME et al. | β | 2006 | β |
| A double-blind, placebo-controlled study of naltrexone in the treatment of alcohol dependence in Taiwan. | Huang MC et al. | β | 2005 | β |
| Aldehyde dehydrogenase (ALDH2) activity in hepatoma cells is reduced by an adenoviral vector coding for an ALDH2 antisense mRNA. | Karahanian E et al. | β | 2005 | β |
| Asians in the United States: substance dependence and use of substance-dependence treatment. | Sakai JT et al. | β | 2005 | β |
| Complex I regulates mutant mitochondrial aldehyde dehydrogenase activity and voluntary ethanol consumption in rats. | Quintanilla ME et al. | β | 2005 | β |
| Considerable haplotype diversity within the 23kb encompassing the ADH7 gene. | Han Y et al. | β | 2005 | β |
| Development of medications for alcohol use disorders: recent advances and ongoing challenges. | Litten RZ et al. | β | 2005 | β |
| Genetic associations of alcohol and aldehyde dehydrogenase with alcohol dependence and their mechanisms of action. | Wall TL | β | 2005 | β |
| Genetic associations of alcohol dehydrogenase with alcohol use disorders and endophenotypes in white college students. | Wall TL et al. | β | 2005 | β |
| Genetic polymorphism of aldehyde dehydrogenase 2 (ALDH2) in a Chinese population: gender, age, culture, and genotypes of ALDH2. | Luo HR et al. | β | 2005 | β |
| [Genetic susceptibility to the development of acute alcoholic hepatitis: role of genetic mutations in dehydrogenase alcohol, aldehyde dehydrogenase and cytochrome P450 2E1]. | Segado Soriano A et al. | β | 2005 | β |
| No alcoholism-protection effects of ADH1B*2 allele in antisocial alcoholics among Han Chinese in Taiwan. | Lu RB et al. | β | 2005 | β |
| Polyamines stimulate the formation of mutagenic 1,N2-propanodeoxyguanosine adducts from acetaldehyde. | Theruvathu JA et al. | β | 2005 | β |
| Polymorphisms in the mitochondrial aldehyde dehydrogenase gene (Aldh2) determine peak blood acetaldehyde levels and voluntary ethanol consumption in rats. | Quintanilla ME et al. | β | 2005 | β |
| Psychosocial, cultural and genetic influences on alcohol use in Asian American youth. | Hendershot CS et al. | β | 2005 | β |
| Rapid, accurate genotyping of alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 based on the use of denaturing HPLC. | Li L et al. | β | 2005 | β |
| Scanning of genetic effects of alcohol metabolism gene (ADH1B and ADH1C) polymorphisms on the risk of alcoholism. | Choi IG et al. | β | 2005 | β |
| The ADH1C polymorphism modifies the risk of squamous cell carcinoma of the head and neck associated with alcohol and tobacco use. | Peters ES et al. | β | 2005 | β |
| The contribution of genetics to addiction therapy approaches. | Edenberg HJ et al. | β | 2005 | β |
| The level of response to alcohol in daughters of alcoholics and controls. | Eng MY et al. | β | 2005 | β |
| World Health Organization/International Society for Biomedical Research on Alcoholism study on state and trait markers of alcohol use and dependence: back to the future. | Wurst FM et al. | β | 2005 | β |
| ADH1B*1, ADH1C*2, DRD2 (-141C Ins), and 5-HTTLPR are associated with alcoholism in Mexican American men living in Los Angeles. | Konishi T et al. | β | 2004 | β |
| Alcohol dehydrogenase polymorphisms influence alcohol-elimination rates in a male Jewish population. | Neumark YD et al. | β | 2004 | β |
| Alcoholism: genes and mechanisms. | Oroszi G et al. | β | 2004 | β |
| ALDH2 status and conduct disorder mediate the relationship between ethnicity and alcohol dependence in Chinese, Korean, and White American college students. | Luczak SE et al. | β | 2004 | β |
| Association of polymorphisms in nicotinic acetylcholine receptor alpha 4 subunit gene (CHRNA4), mu-opioid receptor gene (OPRM1), and ethanol-metabolizing enzyme genes with alcoholism in Korean patients. | Kim SA et al. | β | 2004 | β |
| Biological and behavioral markers of alcohol sensitivity. | Fromme K et al. | β | 2004 | β |
| Drug addiction: the neurobiology of behaviour gone awry. | Volkow ND et al. | β | 2004 | β |
| Functionality of allelic variations in human alcohol dehydrogenase gene family: assessment of a functional window for protection against alcoholism. | Lee SL et al. | β | 2004 | β |
| Genetic polymorphism in ethanol metabolism: acetaldehyde contribution to alcohol abuse and alcoholism. | Quertemont E | β | 2004 | β |
| Genetic polymorphisms of ADH2, ADH3, CYP4502E1 Dra-I and Pst-I, and ALDH2 in Spanish men: lack of association with alcoholism and alcoholic liver disease. | Vidal F et al. | β | 2004 | β |
| Influence of genetic variations of ethanol-metabolizing enzymes on phenotypes of alcohol-related disorders. | Higuchi S et al. | β | 2004 | β |
| Possible epistatic role of ADH7 in the protection against alcoholism. | Osier MV et al. | β | 2004 | β |
| Possible interaction of alcohol dehydrogenase and aldehyde dehydrogenase genes with the dopamine D2 receptor gene in anxiety-depressive alcohol dependence. | Huang SY et al. | β | 2004 | β |
| Acetaldehyde, microbes, and cancer of the digestive tract. | Salaspuro MP | β | 2003 | β |
| Alcohol consumption and cancer of the gastrointestinal tract. | Salaspuro MP | β | 2003 | β |
| Allelic variation at alcohol metabolism genes ( ADH1B, ADH1C, ALDH2) and alcohol dependence in an American Indian population. | Mulligan CJ et al. | β | 2003 | β |
| Approaches to identify genes for complex human diseases: lessons from Mendelian disorders. | Dean M | β | 2003 | β |
| Candidate genes for alcohol dependence: a review of genetic evidence from human studies. | Dick DM et al. | β | 2003 | β |
| Duplex polymerase chain reaction with confronting two-pair primers (PCR-CTPP) for genotyping alcohol dehydrogenase beta subunit (ADH2) and aldehyde dehydrogenase 2 (ALDH2). | Tamakoshi A et al. | β | 2003 | β |
| Neither antisocial personality disorder nor antisocial alcoholism is associated with the MAO-A gene in Han Chinese males. | Lu RB et al. | β | 2003 | β |
| Protective association of genetic variation in alcohol dehydrogenase with alcohol dependence in Native American Mission Indians. | Wall TL et al. | β | 2003 | β |
| The ADH3*2 and CYP2E1 c2 alleles increase the risk of alcoholism in Mexican American men. | Konishi T et al. | β | 2003 | β |
| Use of an "acetaldehyde clamp" in the determination of low-KM aldehyde dehydrogenase activity in H4-II-E-C3 rat hepatoma cells. | Moncada C et al. | β | 2003 | β |
| A proline-threonine substitution in codon 351 of ADH1C is common in Native Americans. | Osier MV et al. | β | 2002 | β |
| Binge drinking in Jewish and non-Jewish white college students. | Luczak SE et al. | β | 2002 | β |
| Genetic contributions to addiction. | Crabbe JC | β | 2002 | β |
| Influence of ADH1B polymorphism on alcohol use and its subjective effects in a Jewish population. | Carr LG et al. | β | 2002 | β |
| Mapping of quantitative trait loci underlying ethanol metabolism in BXD recombinant inbred mouse strains. | Grisel JE et al. | β | 2002 | β |
| Multi-locus interactions predict risk for post-PTCA restenosis: an approach to the genetic analysis of common complex disease. | Zee RY et al. | β | 2002 | β |
| No association of the MAOA gene with alcoholism among Han Chinese males in Taiwan. | Lu RB et al. | β | 2002 | β |
| Technologies for individual genotyping: detection of genetic polymorphisms in drug targets and disease genes. | Shi MM | β | 2002 | β |
| The genetics of alcoholism in Polynesians: alcohol and aldehyde dehydrogenase genotypes in young men. | Chambers GK et al. | β | 2002 | β |
| ADH2 and alcohol-related phenotypes in Ashkenazic Jewish American college students. | Shea SH et al. | β | 2001 | β |
| A genetic association with the development of alcohol and other substance use behavior in Asian Americans. | Wall TL et al. | β | 2001 | β |
| Alcohol and upper gastrointestinal tract cancer: the role of local acetaldehyde production. | Homann N | β | 2001 | β |
| Alcohol dehydrogenase-2*2 allele is associated with decreased prevalence of fetal alcohol syndrome in the mixed-ancestry population of the Western Cape Province, South Africa. | Viljoen DL et al. | β | 2001 | β |
| Association of the ADH2 genotypes with skin responses after ethanol exposure in Japanese male university students. | Takeshita T et al. | β | 2001 | β |
| Binge drinking in Chinese, Korean, and White college students: genetic and ethnic group differences. | Luczak SE et al. | β | 2001 | β |
| Dopamine D2 receptor gene (DRD2) is associated with alcoholism with conduct disorder. | Lu RB et al. | β | 2001 | β |
| Fatal hemolysis after high-dose etoposide: is benzyl alcohol to blame? | Smith AL et al. | β | 2001 | β |
| Functional relevance of human adh polymorphism. | Eriksson CJ et al. | β | 2001 | β |
| Genetic and environmental influences on alcohol metabolism in humans. | Li TK et al. | β | 2001 | β |
| Genetic polymorphisms of alcohol metabolizing enzymes. | Agarwal DP | β | 2001 | β |
| Multipoint development of the weighted pairwise correlation (WPC) linkage method for pedigrees of arbitrary size and application to the analysis of breast cancer and alcoholism familial data. | Zinn-Justin A et al. | β | 2001 | β |
| Research advances in ethanol metabolism. | Ramchandani VA et al. | β | 2001 | β |
| The role of acetaldehyde in the actions of alcohol (update 2000). | Eriksson CJ | β | 2001 | β |
| Variation in alcohol pharmacokinetics as a risk factor for alcohol dependence. | Whitfield JB et al. | β | 2001 | β |
| Genetic polymorphism of alcohol dehydrogenase in europeans: the ADH2*2 allele decreases the risk for alcoholism and is associated with ADH3*1. | BorrΓ s E et al. | β | 2000 | β |
| Kinetic cooperativity of human liver alcohol dehydrogenase gamma(2). | Charlier HA et al. | β | 2000 | β |
| No sex and age influence on the expression pattern and activities of human gastric alcohol and aldehyde dehydrogenases. | Lai CL et al. | β | 2000 | β |
| Pharmacogenetics of the alcohol dehydrogenase system. | JΓΆrnvall H et al. | β | 2000 | β |
| Alcohol metabolism and cardiovascular response in an alcoholic patient homozygous for the ALDH2*2 variant gene allele. | Chen YC et al. | β | 1999 | β |