Association between heroin dependence and prodynorphin gene polymorphisms

Dynorphin peptides and k-opioid receptor are important in the rewarding effects of drugs of abuse such as heroin. This study examined potential association between heroin dependence and four single nucleotide polymorphisms (SNPs) of prodynorphin (PDYN) gene (rs35286281 in promoter region and rs1022563, rs2235749, rs910080 in 3'UTR). Participants included 304 heroin-dependent subjects and 300 healthy controls. Genotype, allele frequencies and difference between groups were analyzed by HaploView 4.0 and SPSS 11.5 software. The analysis indicated a significant higher frequency of the PDYN 68bp VNTR (rs35286281) H allele in heroin-dependent subjects than in controls (p= 0.002 after Bonferroni correction). Strong linkage disequilibrium was observed between rs1022563, rs2235749 and rs910080 polymorphism (D'. >. 0.9). Significantly more TCT haplotypes were found in heroin-dependent patients than in the controls (p= 0.006 after Bonferroni correction). We found significant pointwise correlation of these three variants (rs1022563, rs2235749 and rs910080) with heroin dependence. These findings support the important role of PDYN polymorphism in heroin dependence, and may guide future studies to identify genetic risk factors for heroin dependence.