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. 2014 Jan;76 Pt B(0 0):592-9.
doi: 10.1016/j.neuropharm.2013.09.009. Epub 2013 Sep 18.

A glimpse into the future - Personalized medicine for smoking cessation

Laura Jean Bierut  1 , Eric O Johnson, Nancy L Saccone
Affiliations

A glimpse into the future - Personalized medicine for smoking cessation

Laura Jean Bierut et al. Neuropharmacology. 2014 Jan.

Abstract

The devastating consequences of tobacco smoking for individuals and societies motivate studies to identify and understand the biological pathways that drive smoking behaviors, so that more effective preventions and treatments can be developed. Cigarette smokers respond to nicotine in different ways, with a small number of smokers remaining lifelong low-level smokers who never exhibit any symptoms of dependence, and a larger group becoming nicotine dependent. Whether or not a smoker transitions to nicotine dependence has clear genetic contributions, and variants in the genes encoding the α5-α3-β4 nicotinic receptor subunits most strongly contribute to differences in the risk for developing nicotine dependence among smokers. More recent work reveals a differential response to pharmacologic treatment for smoking cessation based on these same genetic variants in the α5-α3-β4 nicotinic receptor gene cluster. We anticipate a continuing acceleration of the translation of genetic discoveries into more successful treatment for smoking cessation. Given that over 400,000 people in the United States and over 5 million people world-wide die each year from smoking related illnesses, an improved understanding of the mechanisms underlying smoking behavior and smoking cessation must be a high public health priority so we can best intervene at both the public health level and the individual level. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'.

Keywords: Genetics; Nicotine dependence; Nicotine metabolizing genes; Nicotinic receptor genes; Smoking cessation.

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Conflict of interest statement

Conflict of interest

Laura J. Bierut is listed as an inventor on Issued U.S. Patent 8,080,371, ‘Markers for Addiction,’ covering the use of certain SNPs in determining the diagnosis, prognosis, and treatment of addiction. Nancy L. Saccone is the spouse of Scott Saccone, who is also listed as an inventor on the above patent.

Figures

Fig. 1
Fig. 1
Smoking behaviors in the COGEND screening sample.
Fig. 2
Fig. 2
Meta-analysis of the association between the rs16969968 genotype (where A is the risk allele) and heavy smoking (cigarettes per day >20) vs. light smoking (cigarettes per day ≤10), stratified by early-onset smoking (age at onset ≤16 years) and late-onset smoking (onset >16 years). Odds ratios (ORs) are given relative to late-onset smokers with the GG genotype. Effect of the interaction between the rs16969968 A allele and early-onset smoking on risk of heavy smoking: OR = 1.16, n = 36,936, P = 0.01. Figure from Hartz et al., 2012.
Fig. 3
Fig. 3
Response to smoking cessation pharmacotherapy varies by CHRNA5 haplotypes. aCHRNA5 haplotypes are associated with failed smoking cessation in the placebo group (Wald χ2 = 7.02, df = 2, p = 0.03). CHRNA5 haplotypes are not associated with smoking cessation outcomes in the treatment group (Wald χ2 = 1.45, df = 2, p = 0.48). The interaction of haplotypes and treatment on abstinence is significant (Wald χ2 = 8.97, df = 2, p = 0.01). [aCHRNA5 haplotypes based on rs16969968 and rs680244 (N = 1073); H1 = G-C (21%); H2 = G–T; (44%) H3 = A–C (35%).] Figure from Chen et al., 2012b.
See this image and copyright information in PMC

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