Nicotinic Acetylcholine Receptor β2 Subunit (CHRNB2) Gene and Short-Term Ability to Quit Smoking in Response to Nicotine Patch

Abstract

Genes coding for nicotinic acetylcholine receptors may influence response to nicotine replacement therapy for smoking cessation. We examined the association of a 3′ untranslated region polymorphism (rs2072661) in the nicotinic acetylcholine receptor β2 subunit (CHRNB2) gene with quitting success in response to nicotine versus placebo patch during a short-term test of patch effects. In a within-subjects cross-over design, smokers of European descent (n = 156) received 21 mg nicotine and placebo patch in counter-balanced order, during two separate 5-day simulated quit attempts, each preceded by a week of ad libitum smoking. Abstinence was assessed daily by CO < 5 ppm. Smokers with the CHRNB2 GG genotype had more days of abstinence during the nicotine versus placebo patch week compared with those with the AG or AA genotypes (P < 0.01). Moreover, nicotine patch increased the probability of quitting on the target quit day, quitting anytime during the patch week, and avoiding relapse among those with the GG genotype but not the AA/AG genotypes, although the nicotine × genotype interaction was significant only for quitting on the target quit day (P < 0.05). Regardless of patch condition, quitting on the target quit day was more likely in those with the GG genotype versus AA/AG genotypes (P < 0.05). Genetic associations were not observed for craving or withdrawal responses to nicotine versus placebo patch. These findings are consistent with previous evidence of association of this variant with smoking cessation and suggest that polymorphisms in the nicotinic acetylcholine receptor β2 subunit gene may influence therapeutic responsiveness to cessation medications. (Cancer Epidemiol Biomarkers Prev 2009; 18(10):2608-12)

Resequencing of Nicotinic Acetylcholine Receptor Genes and Association of Common and Rare Variants with the Fagerström Test for Nicotine Dependence

“…An analysis of 417 treatment-seeking smokers from a placebo-controlled randomized clinical trial of bupropion and placebo (Lerman et al, 2006) reported significant associations with CHRNB2 SNPs rs2072660 and rs2072661 and abstinence in a logistic model incorporating main effects and interaction with treatment at the end of treatment (P ¼ 0.01) and at 6 months (P ¼ 0.0002) (Conti et al, 2008). A short-term test of nicotine vs placebo patch effects in 156 smokers reported a significant association between rs2072661 and the number of abstinent days (Perkins et al, 2009). In an analysis of CHRNA4 and CHRNB2 SNPs in a sample of 1068 older adolescents, rs2072660 was reported to be significantly associated with sensitivity to tobacco (subjective effects of 'nauseous' or 'dizzy') (Ehringer et al, 2007).…”

Environmental and Genomic Factors as well as Interventions Influencing Smoking Cessation: A Systematic Review of Reviews and a Proposed Working Model

“…Gene-gene interactions are reported between DRD2 Taq1A- SLC6A3 VNTR [40] and DRD2 Taq1A- CYP2B6 C1459T [47]. The variant CHRNB2 rs2072661, which encodes for a nicotinic receptor is associated with SC [51,52]. However, this finding is not replicated in the study of Spruell et al [53].…”

“…Some gene-treatment interactions have been reported in European ancestries. Interactions with nicotine replacement therapy are observed for OPRM1 A118G [36], DRD4 VNTR [48], COMT Val 108/158 Met [43], CHRNB2 rs2072661 [52], and GALR1 rs2717162 [55]. Bupropion interacts with SLC6A4 5-HTTLPR [34], DRD2 TaqIA [42,47], DRD2- 141C [41], DRD4 VNTR [45], CYP2B6 *6 [120], and GALR1 rs2717162 [55].…”

The possible role of maternal bonding style and CHRNB2 gene polymorphisms in nicotine dependence and related depressive phenotype

“…There are some positive findings with rs2072661, which is in strong linkage with rs2072660 in association with smoking behavior. Perkins et al (2009) found that rs2072661 was associated with a greater number of days of nicotine abstinence during patch therapy. In a gene-gene interaction study, rs2072661 had a significant effect on FTND in interaction with CHRNA4 and NTRK2 genes .…”