Association of a variant in the muscarinic acetylcholine receptor 2 gene (CHRM2) with nicotine addiction.
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.
Mobascher
A
A
Department of Psychiatry, Neuropsychiatric Research Laboratory, Heinrich-Heine University, Duesseldorf, Germany.|Institute of Neurosciences and Biophysics, Helmholtz Research Center, Juelich, Germany.
Rujescu
D
D
Department of Psychiatry, Division of Molecular and Clinical Neurobiology, Ludwig-Maximilians-University, Munich, Germany.|Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany.
Mittelstraß
K
K
Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Institute of Epidemiology, Neuherberg, Germany.
Giegling
I
I
Department of Psychiatry, Division of Molecular and Clinical Neurobiology, Ludwig-Maximilians-University, Munich, Germany.|Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany.
Lamina
C
C
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.
Nitz
B
B
Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Institute of Epidemiology, Neuherberg, Germany.
Brenner
H
H
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
Fehr
C
C
Department of Psychiatry, University of Mainz, Mainz, Germany.
Breitling
L P
LP
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
Gallinat
J
J
Department of Psychiatry, Charité University Medicine Berlin, Campus Mitte, Berlin, Germany.
Rothenbacher
D
D
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
Raum
E
E
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
Müller
H
H
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
Ruppert
A
A
Genetics Research Centre GmbH, Munich, Germany.
Hartmann
A M
AM
Department of Psychiatry, Division of Molecular and Clinical Neurobiology, Ludwig-Maximilians-University, Munich, Germany.|Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany.
Möller
H J
HJ
Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany.
Gal
A
A
Institute for Human Genetics, University of Hamburg Medical Center Eppendorf, Hamburg, Germany.
Gieger
Ch
C
Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Institute of Epidemiology, Neuherberg, Germany.
Wichmann
H E
HE
Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Institute of Epidemiology, Neuherberg, Germany.
Illig
T
T
Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Institute of Epidemiology, Neuherberg, Germany.
Dahmen
N
N
Department of Psychiatry, University of Mainz, Mainz, Germany.
Winterer
G
G
Department of Psychiatry, Neuropsychiatric Research Laboratory, Heinrich-Heine University, Duesseldorf, Germany.|Institute of Neurosciences and Biophysics, Helmholtz Research Center, Juelich, Germany.
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*
C487078:CHRM2 protein, human; D043585:Receptor, Muscarinic M2; D009538:Nicotine