title: Association of a variant in the muscarinic acetylcholine receptor 2 gene (CHRM2) with nicotine addiction.
abstract: 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.
authors: Department of Psychiatry, Neuropsychiatric Research Laboratory, Heinrich-Heine University, Duesseldorf, Germany.|Institute of Neurosciences and Biophysics, Helmholtz Research Center, Juelich, Germany.
authors: A
authors: A
authors: Mobascher
authors: Department of Psychiatry, Division of Molecular and Clinical Neurobiology, Ludwig-Maximilians-University, Munich, Germany.|Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany.
authors: D
authors: D
authors: Rujescu
authors: Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Institute of Epidemiology, Neuherberg, Germany.
authors: K
authors: K
authors: Mittelstraß
authors: Department of Psychiatry, Division of Molecular and Clinical Neurobiology, Ludwig-Maximilians-University, Munich, Germany.|Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany.
authors: I
authors: I
authors: Giegling
authors: Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Institute of Epidemiology, Neuherberg, Germany.|Department of Medical Genetics, Molecular and Clinical Pharmacology, Division of Genetic Epidemiology, Innsbruck Medical University, Innsbruck, Austria.
authors: C
authors: C
authors: Lamina
authors: Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Institute of Epidemiology, Neuherberg, Germany.
authors: B
authors: B
authors: Nitz
authors: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
authors: H
authors: H
authors: Brenner
authors: Department of Psychiatry, University of Mainz, Mainz, Germany.
authors: C
authors: C
authors: Fehr
authors: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
authors: L P
authors: LP
authors: Breitling
authors: Department of Psychiatry, Charité University Medicine Berlin, Campus Mitte, Berlin, Germany.
authors: J
authors: J
authors: Gallinat
authors: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
authors: D
authors: D
authors: Rothenbacher
authors: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
authors: E
authors: E
authors: Raum
authors: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
authors: H
authors: H
authors: Müller
authors: Genetics Research Centre GmbH, Munich, Germany.
authors: A
authors: A
authors: Ruppert
authors: Department of Psychiatry, Division of Molecular and Clinical Neurobiology, Ludwig-Maximilians-University, Munich, Germany.|Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany.
authors: A M
authors: AM
authors: Hartmann
authors: Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany.
authors: H J
authors: HJ
authors: Möller
authors: Institute for Human Genetics, University of Hamburg Medical Center Eppendorf, Hamburg, Germany.
authors: A
authors: A
authors: Gal
authors: Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Institute of Epidemiology, Neuherberg, Germany.
authors: Ch
authors: C
authors: Gieger
authors: Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Institute of Epidemiology, Neuherberg, Germany.
authors: H E
authors: HE
authors: Wichmann
authors: Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Institute of Epidemiology, Neuherberg, Germany.
authors: T
authors: T
authors: Illig
authors: Department of Psychiatry, University of Mainz, Mainz, Germany.
authors: N
authors: N
authors: Dahmen
authors: Department of Psychiatry, Neuropsychiatric Research Laboratory, Heinrich-Heine University, Duesseldorf, Germany.|Institute of Neurosciences and Biophysics, Helmholtz Research Center, Juelich, Germany.
authors: G
authors: G
authors: Winterer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000378:metabolism*; D043585:Receptor, Muscarinic M2 / Q000235:genetics*; D012907:Smoking; D014029:Tobacco Use Disorder / Q000235:genetics*
chemical_list: C487078:CHRM2 protein, human; D043585:Receptor, Muscarinic M2; D009538:Nicotine