title: Serotonin transporter promoter polymorphism and monoamine oxidase type A VNTR allelic variants together influence alcohol binge drinking risk in young women.
abstract: The short allelic variant of the serotonin transporter protein promoter polymorphism (5HTTLPR) appears to influence binge drinking in college students. Both monoamine oxidase type A (MAOA) and the serotonin transporter protein are involved in the processing of serotonin, and allelic variants are both associated with differences in the efficiency of expression. We hypothesized that a significant gene x gene interaction would further stratify the risk of binge drinking in this population. Participants were college students (n = 412) who completed the College Alcohol Study, used to measure binge drinking behaviors. Genomic DNA was extracted from saliva for PCR based genotyping. The risk function for binge drinking was modeled using logistic regression, with final model fit P < 0.0005. This model was valid only for Caucasian females (n = 223), but the power to detect sex and ethnic effects was small. Young Caucasian women carrying higher expression MAOA VNTR alleles homozygous for the short allelic variant of the 5HTTLPR demonstrated the highest rate of binge drinking by self-report, odds ratio (genotype odds: population odds) and 95% confidence intervals, 3.11 (1.14-18.10). Individuals carrying higher expression MAOA VNTR alleles carrying at least one long 5HTTLPR allelic variant had the lowest risk of binge drinking 0.46 (0.28-0.71). These results support the hypothesis that binge drinking behavior in young adulthood may be influenced by neurobiological differences in serotonergic function conferred by functional polymorphisms in genes involved in serotonin processing.
authors.affiliation: Unit of Clinical and Biochemical Pharmacology, Laboratory of Clinical Studies, Intramural Research Program, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Aryeh I
authors.initials: AI
authors.lastname: Herman
authors.forename: Kristi M
authors.initials: KM
authors.lastname: Kaiss
authors.forename: Rui
authors.initials: R
authors.lastname: Ma
authors.forename: John W
authors.initials: JW
authors.lastname: Philbeck
authors.forename: Asfar
authors.initials: A
authors.lastname: Hasan
authors.forename: Humza
authors.initials: H
authors.lastname: Dasti
authors.forename: Paolo B
authors.initials: PB
authors.lastname: DePetrillo
mesh_terms: D000293:Adolescent; D000328:Adult; D000428:Alcohol Drinking / Q000208:ethnology / Q000235:genetics*; D000483:Alleles; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics*; D018598:Minisatellite Repeats / Q000235:genetics*; D008995:Monoamine Oxidase / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins; D012737:Sex Factors
chemical_list: D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D008995:Monoamine Oxidase