ASSOCIATION STUDY OF DRD2 AND DRD4 GENES POLYMORPHISM WITH ALCOHOLISM AND HEROIN ADDICTION
Molecular genetics data analysis suggests existence of genetic predisposition to psychoactive substance dependence, and identification of its determinants is the goal of molecular genetic research in addictology. Chronic dysfunction of brain dopaminergetic neurotransmitter system is thought to be the neurochemical background of psychoactive substance dependence phenomenon, and first of all it involves reinforcement system. Clinical implications of psychoactive substance dependence represent itself as a super-complex "mosaic" phenotype defined by multiple interaction of genes, primarily of dopaminergetic neurotransmitter system. In this context, D2 and D4 receptor genes are of the main interest due to their functional role. This association study aimed to investigate dopamine receptors DRD2 (Taq I, NcOI) and DRD4 (48 bp VNTR) genes polymorphic loci structure in patients with alcoholism (n=252) and heroin addiction (n=326) in comparison with control group (n=141). RESULTS. DRD2 gene. Patients with alcoholism (A) and drug addiction (H) showed similar and unidirectional frequency variation when compared to controls (K): prevalence of the Al allele frequency (A - 20,77%, И - 23,51% (p=0,018) vs. К - 16,41%), increase in the frequencies of A 1\A2 genotype (A - 31,05% (Pb=0,058), H - 39,5% (Pb=0,0002) vs. K- 20,6%) and tandem genotype for two loci (Taq+NcO) (AI\A2,N1\N1): A - 18,95% (Pb=0,0488), H - 19,3% (Pb=0,0006) vs. К - 9,9%. DRD4 gene. Significant reduction of alleles cluster (A2+A3+A8) frequency was found in patients: A - 13,5% (Pb=0,009), H- 11,5% (Pb=0,004) vs. К-21,6%. Prevalence of genotype cluster(2\7+ 4\4+4\5+4\7) frequency in groups of patients : A - 80% (Pb=0,023), H - 85% (Pb=0,011, OR=2,41 [1,31; 4,44]), К - 68%. The fact that the revealed gene determinants are universal for different kinds of psychoactive substance dependence (alcohol and heroin in our case) may indicate pathogenetic character of this "system" of determinants, probably associated with genetic predisposition to addiction diseases.