Association between three common genetic polymorphisms of XPC and susceptibility to heroin dependency

Abstract

As heroin and morphine produce reactive oxygen species and down-regulate several genes involved in cellular detoxification and DNA repair pathways, neurons experience DNA damage. Xeroderma pigmentosum complementation group C (XPC, OMIM: 613208) gene, which is expressed in the brain, is one of the central genes in the nucleotide excision repair pathway. Three common XPC polymorphisms (Lys939Gln, Ala499Val and PAT) are associated with reduced DNA repair capacity. In this study, the relationship between these polymorphisms and the risk of heroin dependency (HD), as well as, age of first use (AFU) for illegal drugs was investigated on 795 healthy individuals and 442 heroin dependent patients. Statistical analyses indicated that there was no significant association between the XPC polymorphisms and the risk of HD. The haplotypic frequencies of the polymorphisms showed significant difference between HD patients and healthy controls (χ² = 16.38, df = 6, P = 0.012). Analysis indicated that the "Ala + Gln" haplotype increased the HD risk more than the "Ala + Lys" haplotype (OR = 4.21, 95% CI = 1.29-13.7, P = 0.017). In Cox proportional model, there was significant association between AFU and the Ala499Val polymorphism (Hazard ratio = 1.53, 95% CI: 1.02-2.92, P = 0.036). To investigate the effect of the linkage between the polymorphic sites, we compared the AFU among two common diplotypes ("Ala - Lys/Ala - Lys" and "Val - Lys/Val - Lys"). Statistical analysis indicated that AFU was significantly lower in "Val - Lys/Val - Lys" diplotype (t = 2.63, df = 49, P = 0.011). The present findings suggest that the XPC is a candidate polymorphic locus for AFU.

Keywords: Drug dependency; Genetic polymorphism; XPC.