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Variants in nicotinic acetylcholine receptors α5 and α3 increase risks to nicotine dependence
Author(s) -
Chen Xiangning,
Chen Jingchun,
Williamson Vernell S.,
An SeonSook,
Hettema John M.,
Aggen Steven H.,
Neale Michael C.,
Kendler Kenneth S.
Publication year - 2009
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.30919
Subject(s) - nicotine , nicotinic agonist , alcohol dependence , cannabis dependence , cannabis , nicotinic acetylcholine receptor , alcohol , acetylcholine receptor , single nucleotide polymorphism , nicotine dependence , pharmacology , medicine , chemistry , receptor , genetics , psychiatry , biology , gene , genotype , biochemistry , cannabidiol
Nicotinic acetylcholine receptors bind to nicotine and initiate the physiological and pharmacological responses to tobacco smoking. In this report, we studied the association of α5 and α3 subunits with nicotine dependence and with the symptoms of alcohol and cannabis abuse and dependence in two independent epidemiological samples (n = 815 and 1,121, respectively). In this study, seven single nucleotide polymorphisms were genotyped in the CHRNA5 and CHRNA3 genes. In both samples, we found that the same alleles of rs16969968 ( P = 0.0068 and 0.0028) and rs1051730 ( P = 0.0237 and 0.0039) were significantly associated with the scores of Fagerström test for nicotine dependence (FTND). In the analyses of the symptoms of abuse/dependence of alcohol and cannabis, we found that rs16969968 and rs1051730 were significantly associated with the symptoms of alcohol abuse or dependence ( P = 0.0072 and 0.0057) in the combined sample, but the associated alleles were the opposite of that of FTND. No association with cannabis abuse/dependence was found. These results suggested that the α5 and α3 subunits play a significant role in both nicotine dependence and alcohol abuse/dependence. However, the opposite effects with nicotine dependence and alcohol abuse/dependence were puzzling and future studies are necessary to resolve this issue. © 2009 Wiley‐Liss, Inc.