Interplay of genetic risk factors (CHRNA5-CHRNA3-CHRNB4) and cessation treatments in smoking cessation success.
paper
Primary
Public
- Authors
- Chen, Li-Shiun; Baker, Timothy B; Piper, Megan E; Breslau, Naomi; Cannon, Dale S; Doheny, Kimberly F; Gogarten, Stephanie M; Johnson, Eric O; Saccone, Nancy L; Wang, Jen C; Weiss, Robert B; Goate, Alison M; Bierut, Laura Jean
- Year
- 2012
- Journal
- The American journal of psychiatry
- PMID
- 22648373
- DOI
- 10.1176/appi.ajp.2012.11101545
- PMCID
- PMC3433845
OBJECTIVE: Smoking is highly intractable, and the genetic influences on cessation are unclear. Identifying the genetic factors affecting smoking cessation could elucidate the nature of tobacco dependence, enhance risk assessment, and support development of treatment algorithms. This study tested whether variants in the nicotinic receptor gene cluster CHRNA5-CHRNA3-CHRNB4 predict age at smoking cessation and relapse after an attempt to quit smoking. METHOD: In a community-based, crosssectional study (N=5,216) and a randomized comparative effectiveness smoking cessation trial (N=1,073), the authors used Cox proportional hazard models and logistic regression to model the relationships of smoking cessation (self-reported quit age in the community study and point-prevalence abstinence at the end of treatment in the clinical trial) to three common haplotypes in the CHRNA5-CHRNA3-CHRNB4 region defined by rs16969968 and rs680244. RESULTS: The genetic variants in the CHRNA5-CHRNA3-CHRNB4 region that predict nicotine dependence also predicted a later age at smoking cessation in the community sample. In the smoking cessation trial, haplotype predicted abstinence at end of treatment in individuals receiving placebo but not among individuals receiving active medication. Haplotype interacted with treatment in affecting cessation success. CONCLUSIONS: Smokers with the high-risk haplotype were three times as likely to respond to pharmacologic cessation treatments as were smokers with the low-risk haplotype. The high-risk haplotype increased the risk of cessation failure, and this increased risk was ameliorated by cessation pharmacotherapy. By identifying a high-risk genetic group with heightened response to smoking cessation pharmacotherapy, this work may support the development of personalized cessation treatments.
Interaction of Haplotypic Risk and Treatment Effect on Abstinence at End-of-TreatmentThe interaction of haplotypes and treatment on abstinence is significant (X2=8.97, df=2, p=0.011).Abstinence is defined at end of 8 Week treatment. Odds ratios are adjusted for age and gender.Haplotypes based on 2 SNPs (rs16969968, rs680244): H1=GC(20.8%), H2=GT(43.7%), H3=AC(35.5%).N=1073 (132 in the placebo group; 941 in the treatment group).
LLM interpretation
This grouped bar chart displays the odds ratios (OR) for abstinence at the end of an 8-week treatment across three haplotypes (H1, H2, and H3), comparing a placebo group (yellow) to a treatment group (green). H1 serves as the reference group, while the treatment group shows higher ORs for abstinence in H2 (1.11) and H3 (1.13) compared to the placebo group (0.62 and 0.37, respectively). The y-axis represents the OR for abstinence, and the x-axis categorizes the three haplotypes.
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