title: Association of VMAT2 gene polymorphisms with alcohol dependence.
abstract: Alcohol-related diseases cause significant harm in the western world. Up to 65 % of the phenotypic variance is genetically determined. Few candidate genes have been identified, comprising ADH4, ALDH2, COMT, CRHR1, DAT (SLC6A3), GABRA2 and MAOA. While abnormalities in the dopaminergic mesolimbic reward system are considered important mediators of alcoholism, studies analyzing variants of dopamine receptors showed conflicting results. Other modulators of the reward system are synaptosomal genes. Among candidate genes, polygenic variants of the Vesicular Monamine Transporter 2 (VMAT2) gene locus associated with alterations of drinking behavior were published. These variants comprise single nucleotide polymorphisms (SNPs) within the promoter region and the open reading frame. In this study, we confirm the association of VMAT2 SNP rs363387 (allelic association: p = 0.015) with alcohol dependence. This SNP defines several haplotypes including up to four SNPs (minimal p = 0.0045). In addition, numeric effects in the subgroups of males and patients with positive family history were found. We suggest that several rs363387 T-allele containing haplotypes increase the risk of alcohol dependence (OR 1.53), whereas G-allele containing haplotypes confer protection against alcohol dependence. Taken together, there is supporting evidence for a contribution of VMAT2 gene variants to phenotypes of alcohol dependence.
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Mainz, Untere Zahlbacher Str. 8, 55131, Mainz, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Fehr
authors.forename: Daniel
authors.initials: D
authors.lastname: Sommerlad
authors.forename: Thomas
authors.initials: T
authors.lastname: Sander
authors.forename: Ion
authors.initials: I
authors.lastname: Anghelescu
authors.forename: Norbert
authors.initials: N
authors.lastname: Dahmen
authors.forename: Armin
authors.initials: A
authors.lastname: Szegedi
authors.forename: Christiana
authors.initials: C
authors.lastname: Mueller
authors.forename: Peter
authors.initials: P
authors.lastname: Zill
authors.forename: Michael
authors.initials: M
authors.lastname: Soyka
authors.forename: Ulrich W
authors.initials: UW
authors.lastname: Preuss
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies / Q000379:methods*; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D050493:Vesicular Monoamine Transport Proteins / Q000235:genetics*
chemical_list: C493452:SLC18A2 protein, human; D050493:Vesicular Monoamine Transport Proteins