title: Epistatic interactions involving DRD2, DRD4, and COMT polymorphisms and risk of substance abuse in women with binge-purge eating disturbances.
abstract: Substance abuse is common in individuals with bulimia-spectrum (binge-purge) eating disturbances, a co-occurrence that has been attributed to shared neurobiological substrates--notably alterations in dopaminergic activity. We examined the implications of variations of selected, dopamine-relevant polymorphisms (DRD2 Taq1A, DRD4 7R, and COMT) for risk of substance abuse in women with binge-purge eating syndromes. We genotyped 183 women (66.1% showing full-threshold BN and 33.9% showing sub-syndromic variants), and assessed lifetime presence of alcohol, cannabis, cocaine, and stimulant abuse or dependence using structured interviews. Tests for main and interaction effects of various allele combinations revealed that individuals who carried high function COMT and low-function DRD4 7R alleles (a combination expected to be associated with higher risk) did indeed show more lifetime substance abuse and, specifically, more cannabis abuse. Our findings suggest that a gene combination that, in theory, codes for low levels of dopaminergic neurotransmission coincides with sensitivity to substance abuse in a sample displaying binge-purge eating-disorder variants.
authors.affiliation: Eating Disorders Program, Douglas University Institute, Canada; Psychiatry Department, McGill University, Canada; Research Centre, Douglas University Institute, Canada. Electronic address: stehow@douglas.mcgill.ca.
authors.forename: Howard
authors.initials: H
authors.lastname: Steiger
authors.affiliation: Eating Disorders Program, Douglas University Institute, Canada; Psychiatry Department, McGill University, Canada; Research Centre, Douglas University Institute, Canada.
authors.forename: Lea
authors.initials: L
authors.lastname: Thaler
authors.affiliation: Research Centre, Douglas University Institute, Canada; Research Centre, University of Montreal Hospital Centre, Canada.
authors.forename: Lise
authors.initials: L
authors.lastname: Gauvin
authors.affiliation: Psychiatry Department, McGill University, Canada; Research Centre, Douglas University Institute, Canada.
authors.forename: Ridha
authors.initials: R
authors.lastname: Joober
authors.affiliation: Psychiatry Department, McGill University, Canada; Research Centre, Douglas University Institute, Canada.
authors.forename: Aurelie
authors.initials: A
authors.lastname: Labbe
authors.affiliation: Eating Disorders Program, Douglas University Institute, Canada; Psychiatry Department, McGill University, Canada; Research Centre, Douglas University Institute, Canada.
authors.forename: Mimi
authors.initials: M
authors.lastname: Israel
authors.affiliation: Eating Disorders Program, Douglas University Institute, Canada.
authors.forename: Audrey
authors.initials: A
authors.lastname: Kucer
mesh_terms: D000293:Adolescent; D000328:Adult; D052018:Bulimia Nervosa / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D012044:Regression Analysis; D012306:Risk; D019966:Substance-Related Disorders / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D055815:Young Adult
chemical_list: C581293:DRD2 protein, human; C493599:DRD4 protein, human; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
keywords: DRD2; DRD4; bulimia nervosa; dopamine; genes; substance abuse