Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Jul;169(7):735-42.
doi: 10.1176/appi.ajp.2012.11101545.

Interplay of genetic risk factors (CHRNA5-CHRNA3-CHRNB4) and cessation treatments in smoking cessation success

Li-Shiun Chen  1 , Timothy B Baker, Megan E Piper, Naomi Breslau, Dale S Cannon, Kimberly F Doheny, Stephanie M Gogarten, Eric O Johnson, Nancy L Saccone, Jen C Wang, Robert B Weiss, Alison M Goate, Laura Jean Bierut
Affiliations

Interplay of genetic risk factors (CHRNA5-CHRNA3-CHRNB4) and cessation treatments in smoking cessation success

Li-Shiun Chen et al. Am J Psychiatry. 2012 Jul.

Abstract

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Interaction of Haplotypic Risk and Treatment Effect on Abstinence at End-of-Treatment
The 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).
See this image and copyright information in PMC

Comment in

References

    1. Breslau N, Johnson EO, Hiripi E, Kessler R. Nicotine dependence in the United States: prevalence, trends, and smoking persistence. Archives of General Psychiatry. 2001;58(9):810–6. [see comment] - PubMed
    1. Hughes JR, Baker T, Breslau N, Covey L, Shiffman S. Applicability of DSM criteria to nicotine dependence. Addiction. 2011;106(5):894–5. discussion 895-7. - PubMed
    1. West R. In: Bock G, Goode J, editors. Defining and assessming nicotine dependence in humans; Understanding nicotine and tobacco addiction Novartis Foundation Symposium, No 275; Chichester, UK: Wiley; 2005. pp. 36–58.
    1. Breslau N, Johnson EO. Predicting smoking cessation and major depression in nicotine-dependent smokers. Am J Public Health. 2000;90(7):1122–7. - PMC - PubMed
    1. Baker TB, Piper ME, McCarthy DE, Bolt DM, Smith SS, Kim SY, Colby S, Conti D, Giovino GA, Hatsukami D, Hyland A, Krishnan-Sarin S, Niaura R, Perkins KA, Toll BA. Time to first cigarette in the morning as an index of ability to quit smoking: implications for nicotine dependence. Nicotine Tob Res. 2007;9(Suppl 4):S555–70. - PMC - PubMed

Publication types

Grants and funding