SY13-2-2 * IMPULSITIVY PERSONALITY TRAITS AND GENE POLYMORPHISMS ASSOCIATED WITH HEROIN DEPENDENCE IN A SRI LANKAN POPULATION

Abstract

We assessed the impulsivity personality traits and nineteen candidate polymorphisms of the GABA, opioid and dopamine pathways of the reward system in 157 Sinhalese, male dependent heroin users and 155 age- and ethnicity-matched extreme controls using direct, indirect and epistatic association analyses. Results using a two-factor model of impulsivity provided novel information about substance-use behaviours. Heroin dependence was associated with both higher rash-impulsiveness and reward sensitivity, while heroin dependence-associated sub-phenotypes like high-risk behaviour that included escalating heroin consumption, injecting heroin use, hazardous drinking, low treatment-seeking, and risky sexual behaviour were associated only with high rash-impulsiveness. An early onset of drug use was associated with reward sensitivity. Using direct, indirect and epistatic associations revealed subtle polygenetic effects. GABA receptor SNPs (GABRG2- rs3219151 and GABRG2-rs211013) showed both individual and haplotype association with heroin dependence. Two opioid mu-receptor SNPs (OPRM1- rs1799971 and OPRM1-rs563649) also showed individual association with heroin dependence. The same GABA SNPs and DRD2-rs1079597 were associated with impulsivity-related traits, which mediated the effect of these polymorphisms on heroin dependence. Further, we found a statistically significant and biologically relevant epistatic interaction between GABRG2 and OPRM1 for risk of heroin dependence. These findings portray novel and plausible potential mechanisms of genetic predisposition to heroin dependence.