Association between genetic polymorphisms of XRCC4 insertion/deletion in intron 3 and G-1394T of XRCC4 and susceptibility to dependency to heroin

Abstract

The ubiquitously expressed X-ray repair cross complementing group 4 (XRCC4, OMIM: 194363) is essential in the non-homologous end-joining pathway. Since genetic polymorphisms in the XRCC4 might be associated with a reduction in cellular DNA repair capacity, it is hypothesized that the XRCC4 G-1394T (rs6869366) and Insertion/Deletion (Ins/Del, polymorphism in intron 3 of the gene; rs28360071) polymorphisms may be a risk factor for heroin dependency (HD). Considering that there is no study on association between the rs6869366 and rs28360071 polymorphisms and the risk of HD, the present case-control study was carried out on 1241 participants (442 heroin dependent subjects and 799 healthy blood donors). The genotypes were determined by PCR based methods. The Ins/Del (OR = 1.41, CI = 1.08–1.85, P = 0.012) and Del/Del (OR = 1.95, CI = 1.39–2.76, P < 0.001) genotypes increased the risk of HD. Analysis of the G-1394T polymorphism showed that the TG genotype significantly decreased the risk of HD (OR = 0.73, CI = 0.54–0.99, P = 0.043). It should be noted that the linear trend between the number of the G allele and the risk of HD was significant (χ2 = 6.42, P = 0.011). The study polymorphisms showed strong linkage disequilibrium in both control and HD patients. There were significant associations between the Ins-G (OR = 0.45, CI = 0.23–0.88, P = 0.020), Ins-T (OR = 0.63, CI = 0.53–0.76, P < 0.001), and Del-G (OR = 0.54, CI = 0.40–0.74, P < 0.001) haplotypes and the risk of HD. These results also suggest that genetic variants of the rs6869366 and rs28360071 polymorphisms are involved in etiology of HD and could be novel markers for HD.