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Genetic variation in CHRNA7 and CHRFAM7A is associated with nicotine dependence and response to varenicline treatment.


ABSTRACT: The role of nicotinic acetylcholine receptors (nAChR) in nicotine dependence (ND) is well established; CHRNA7, encoding the ?7 subunit, has a still uncertain role in ND, although it is implicated in a wide range of neuropsychiatric conditions. CHRFAM7A, a hybrid gene containing a partial duplication of CHRNA7, is possibly involved in modulating ?7 nAChR function. The aim of this study was to investigate the role of CHRNA7 and CHRFAM7A genetic variants in ND and to test the hypothesis that ?7 nAChR variation may modulate the efficacy of varenicline treatment in smoking cessation. We assessed CHRNA7 and CHRFAM7A copy number, CHRFAM7A exon 6 ?2?bp polymorphism, and sequence variants in the CHRNA7 proximal promoter in an Italian sample of 408 treatment-seeking smokers. We conducted case-control and quantitative association analyses using two smoking measures (cigarettes per day, CPD, and Fagerström Test for Nicotine Dependence, FTND). Next, driven by the hypothesis that varenicline may exert some of its therapeutic effects through activation of ?7 nAChRs, we restricted the analysis to a subgroup of 142 smokers who received varenicline treatment. The CHRNA7 promoter variant rs28531779 showed association with both smoking quantitative measures (FNTD p?=?0.026, ??=?0.89, 95% CI 0.11-1.67; CPD p?=?0.006, ??=?4.82 95% CI 1.42-8.22). Moreover, in the varenicline-treated subgroup we observed association of CHRFAM7A copy number with 6 months smoking abstinence (p?=?0.035, OR?=?3.18, 95% CI?=?1.09-9.30). Thus, our study points to a possible role of genetic variation in CHRNA7 and CHRFAM7A in tobacco addiction mechanisms and response to varenicline treatment.

SUBMITTER: Cameli C 

PROVIDER: S-EPMC6244195 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Genetic variation in CHRNA7 and CHRFAM7A is associated with nicotine dependence and response to varenicline treatment.

Cameli Cinzia C   Bacchelli Elena E   De Paola Maria M   Giucastro Giuliano G   Cifiello Stefano S   Collo Ginetta G   Cainazzo Maria Michela MM   Pini Luigi Alberto LA   Maestrini Elena E   Zoli Michele M  

European journal of human genetics : EJHG 20180808 12


The role of nicotinic acetylcholine receptors (nAChR) in nicotine dependence (ND) is well established; CHRNA7, encoding the α7 subunit, has a still uncertain role in ND, although it is implicated in a wide range of neuropsychiatric conditions. CHRFAM7A, a hybrid gene containing a partial duplication of CHRNA7, is possibly involved in modulating α7 nAChR function. The aim of this study was to investigate the role of CHRNA7 and CHRFAM7A genetic variants in ND and to test the hypothesis that α7 nAC  ...[more]

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