Association Study Of Polymorphism In Dopamine Beta Hydroxylase Gene With Heroin Dependence

Heroin addiction is a major threat to global public health. Indeed, heroin dependence is a complex behaviour disorder, resulting from the interaction between multiple genetic and environmental factors. The specific genetic factors are not yet well understood. Elucidating the genetic basic of heroin addiction would promote progress toward understanding the etiology of this complex disorder.We executed a genome-wide scan for the susceptibility loci of heroin addiction using association analysis. 20 independent case-control sibling-pairs from Ningbo of China were recruited and genotyped by PCR method on 400 short tandem repeat (STR) genetic markers spaced at the average distance of 10 cM throughout genome. We found several loci may be associated with heroin addiction, which were D2S396, D9S1776, D9S158, D10S196 and D20S195 (P=0.001). And we also searched out some loci of suggestive evidence for association with heroin dependence (P<0.01).Candidate gene dopamine beta hydroxylase (DBH) located closer to D9S164, a suggestive locus for heroin addiction. DBH catalyzes the conversion of dopamine to norepinephrine and could adjust the ratio of the two neurotransmitters. The -1021C/T polymorphism (rs1611115) in the 5' transcriptional regulatory region of DBH gene has been found to be accounted for about 44% of individual variation in plasma DBH activity. To test the influence of this polymorphism on the susceptibility of heroin dependence, the -1021C/T genotypes of DBH gene of 333 male heroin dependent patients and 200 male controls were detected by PCR-RFLP method, and the association between polymorphism of DBH gene and heroin dependence were analyzed. Genotypic and allelic analyses did not show any evidence of association with heroin addiction (P > 0.05). But in the injection group of heroin dependence, the average daily amount of heroin with TT genotype was higher than that of the other genotypes (P<0.05).Conclusion: The study demonstrated that several loci may be associated with heroin addiction and the candidate genes in these putative susceptibility regions could be verified in future studies. The -1021C/T polymorphism of dopamine beta hydroxylase gene may not play a major role in the development of heroin dependence, but may influence the drug dose of the heroin injecting addicts.