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 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 α7 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, β = 0.89, 95% CI 0.11–1.67; CPD p = 0.006, β = 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.

Genetic variation in CHRNA7 and CHRFAM7A is associated with nicotine dependence and response to varenicline treatment / Cameli, Cinzia; Bacchelli, Elena; De Paola, Maria; Giucastro, Giuliano; Cifiello, Stefano; Collo, Ginetta; Cainazzo, Maria Michela; Pini, Luigi Alberto; Maestrini, Elena; Zoli, Michele. - In: EUROPEAN JOURNAL OF HUMAN GENETICS. - ISSN 1018-4813. - (2018), pp. 1-8. [10.1038/s41431-018-0223-2]

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

De Paola, Maria;Cainazzo, Maria Michela;Pini, Luigi Alberto;Zoli, Michele
2018

Abstract

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 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 α7 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, β = 0.89, 95% CI 0.11–1.67; CPD p = 0.006, β = 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.
8-ago-2018
1
8
Genetic variation in CHRNA7 and CHRFAM7A is associated with nicotine dependence and response to varenicline treatment / Cameli, Cinzia; Bacchelli, Elena; De Paola, Maria; Giucastro, Giuliano; Cifiello, Stefano; Collo, Ginetta; Cainazzo, Maria Michela; Pini, Luigi Alberto; Maestrini, Elena; Zoli, Michele. - In: EUROPEAN JOURNAL OF HUMAN GENETICS. - ISSN 1018-4813. - (2018), pp. 1-8. [10.1038/s41431-018-0223-2]
Cameli, Cinzia; Bacchelli, Elena; De Paola, Maria; Giucastro, Giuliano; Cifiello, Stefano; Collo, Ginetta; Cainazzo, Maria Michela; Pini, Luigi Alberto; Maestrini, Elena; Zoli, Michele
File in questo prodotto:
File Dimensione Formato  
Cameli_CHRNA7_ejhg.pdf

non disponibili

Tipologia: Versione dell'editore (versione pubblicata)
Dimensione 463.63 kB
Formato Adobe PDF
463.63 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/1165919
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 8
  • ???jsp.display-item.citation.isi??? 7
social impact