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Chunk #34 — Nicotinic acetylcholine receptor (nAChR) subunits — CHRNA6- CHRNB3

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Pharmacogenetics of smoking cessation: role of nicotine target and metabolism genes.
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Genetic association studies have shown that SNPs in the genes encoding the α6 and β3 subunits, CHRNA6 and CHRNB3, are associated with nicotine dependence and subjective response to nicotine (Bierut et al. 2007; Greenbaum et al. 2006; Saccone et al. 2007; Zeiger et al. 2008). The role of CHRNA6 and CHRNB3 in smoking cessation was examined by Hoft et al. (2009). They used a family-based approach, genotyping 1,051 subjects (50% members of sibling pairs), to test for an association with quit attempts and overall dependence as measured by DSM-IV dependence scale. The rs7004381, rs4950 and, rs13280604 SNPs in the CHRNB3 gene were associated with self-reported number of unsuccessful quit attempts, while CHRNA6 SNP rs2304297 was associated with nicotine dependence. Replication of associations between specific SNPs and smoking behavior phenotypes has not been easy due to inconsistencies in the definition of a phenotype and the inclusion sample. Hoft et al. (2009) performed secondary analyses with sets of individuals who reported having used tobacco every day for at least 1 month in their lives and the entire sample of 1,051 individuals. The