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Mobascher, A.* ; Rujescu, D.* ; Mittelstraß, K. ; Giegling, I.* ; Lamina, C. ; Nitz, B. ; Brenner, H.* ; Fehr, C.* ; Breitling, L.P.* ; Gallinat, J.* ; Rothenbacher, D.* ; Raum, E.* ; Müller, H.* ; Ruppert, A.* ; Hartmann, A.M.* ; Möller, H.J.* ; Gal, A.* ; Gieger, C. ; Wichmann, H.-E. ; Illig, T. ; Dahmen, N.* ; Winterer, G.*

Association of a variant in the muscarinic acetylcholine receptor 2 gene (CHRM2) with nicotine addiction.

Am. J. Med. Genet. B 153B, 684-690 (2010)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Genetic factors contribute to the overall risk of developing nicotine addiction, which is the major cause of preventable deaths in western countries. However, knowledge regarding specific polymorphisms influencing smoking phenotypes remains scarce. In the present study we provide evidence that a common single nucleotide polymorphism (SNP) in the 5' untranslated region of CHRM2, the gene coding for the muscarinic acetylcholine receptor 2 is associated with nicotine addiction. CHRM2 was defined as a candidate gene for nicotine addiction based on previous evidence that linked variations in CHRM2 to alcohol and drug dependence. A total of more than 5,500 subjects representative of the German population were genotyped and assessed regarding their smoking habits. The impact of three SNPs in CHRM2 on smoking behavior/nicotine addiction was investigated using logistic regression models or a quasi-Poisson regression model, respectively. We found the T allele of SNP rs324650 to be associated with an increased risk of smoking/nicotine dependence according to three different models, the recessive models of regular or heavy smokers vs. never-smokers (odds ratio 1.17 in both analyses) and according to the Fagerström index of nicotine addiction. In the analysis stratified by gender this association was only found in females. Our data provide further evidence that variations in CHRM2 may be associated with the genetic risk of addiction in general or with certain personality traits that predispose to the development of addiction. Alternatively, variations in CHRM2 could modulate presynaptic auto-regulation in cholinergic systems and may thereby affect an individual's response to nicotine more specifically.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Smoking; Nicotine addiction; CHRM2
ISSN (print) / ISBN 1552-4841
e-ISSN 0148-7299
Journal American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Quellenangaben Volume: 153B, Issue: 2, Pages: 684-690 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Hoboken, NJ
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)