Epistatic interactions involving DRD2, DRD4, and COMT polymorphisms and risk of substance abuse in women with binge-purge eating disturbances

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.