Department of Forensic Science, School of Medicine, Xi'an Jiaotong University, Key Laboratory of Ministry of Public Health for Forensic Science, Xi'an, Shannxi, PR China.
Brain Res Bull. 2011 May 30;85(3-4):238-42. doi: 10.1016/j.brainresbull.2011.02.010. Epub 2011 Mar 4.
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.
脑啡肽和 κ 阿片受体在海洛因等滥用药物的奖赏效应中起着重要作用。本研究探讨了强啡肽原（PDYN）基因四个单核苷酸多态性（SNPs）（启动子区 rs35286281 和 3'UTR 区 rs1022563、rs2235749、rs910080）与海洛因依赖之间的潜在关联。参与者包括 304 例海洛因依赖者和 300 例健康对照者。采用 HaploView 4.0 和 SPSS 11.5 软件分析基因型、等位基因频率及组间差异。分析表明，海洛因依赖者 PDYN68bpVNTR（rs35286281）H 等位基因频率明显高于对照组（Bonferroni 校正后 P=0.002）。rs1022563、rs2235749 和 rs910080 多态性之间存在强连锁不平衡（D'＞0.9）。海洛因依赖者 TCT 单倍型明显多于对照组（Bonferroni 校正后 P=0.006）。这三个变异体（rs1022563、rs2235749 和 rs910080）与海洛因依赖呈显著点状相关。这些发现支持 PDYN 多态性在海洛因依赖中的重要作用，并可能指导未来研究确定海洛因依赖的遗传风险因素。
