Anti-OPRK1 (aa 366-380) polyclonal antibody

Prodynorphin (PDYN) binds to k-opioid receptors (KOPr; encoded by OPRK1) and is known to regulate dopaminergic tone, making this system important for drugs addiction. Dynorphin (Dyn)/KORr system are powerful effectors of stress-induced alterations in reward processing and dysphoric states. Thus, We identified 11 potential functional SNPs and one variable number of tandem repeat (VNTR) in this system, performed a case-control association analysis, investigated particular disease phenotypes, assessed the joint effect of variants in two genes, carried out a meta-analysis to analyze the association between this VNTR and Heroin dependence (HD) risk. Eleven single-nucleotide polymorphisms (SNPs) were genotyped using SNaPshot SNP technology. Participants included 566 healthy controls and 541 patients with HD. We found that PDYN polymorphisms modulate the susceptibility to HD. An increased risk of HD was significantly associated with H alleles of PDYN VNTR (chi(2) = 10.824, p = 0.001, OR = 1.419, 95% CI = 1.151-1.748). In addition, the results revealed the patients with the HH genotype showed greater number of withdrawal instances (F(2538) = 7.987, p = 0.0004) compared to the patients with the LL genotype. The Meta-analysis showed the pooled effect of the H allele at this locus is a risk factor for HD in Chinese Han. Gene-gene interaction analysis indicated strong interactions between PDYN rs3830064, 68-bp VNTR and OPRK1 rs16918842, rs3802279. These findings support the important role of PDYN polymorphism in HD, and may guide future studies to identify genetic risk factors for HD.

Heroin and drug dependence are major contributors to global health burden worldwide, but their underlying mechanisms remain elusive and may vary from population to population. Reward-and memory-related candidate genes dopamine D2 receptor (DRD2) and brain-derived neurotrophic factor (BDNF), as well as the opioid receptor genes (OPRM1, OPRD1, and OPRK1), have been implicated in drug dependence, but relatively little is known on their contributions to heroin dependence in populations worldwide. Hence, we evaluated the contributions of the above five candidate genes in heroin dependence and several important related endophenotypes (the onset age of heroin use and subjective response to first heroin use), at single single-nucleotide polymorphism as well as haplotype levels, in a Han Chinese population sample. We genotyped 546 unrelated and heroindependent subjects for the candidate genes noted, and 228 sex-and age-matched unrelated controls. The G allele of rs4654327 (OPRD1), DRD2 haplotype block CCGCCGTT (rs6277-rs1076560-rs2283265-rs2734833-rs 2075652-rs1079596-rs4436578-rs11214607), and OPRD1 haplotypes TACG (rs6669447-rs2236857-rs508448rs4654327), CG (rs508448-rs4654327), and TG (rs6669447-rs4654327) were significantly associated with heroin dependence phenotype. Homozygotes AA at rs6265 (BDNF), TT at rs16917234 (BDNF), and CC at rs508448 (OPRD1) also appeared as risk factors for the endophenotype earlier age of onset for heroin use. Two OPRM1 haplotypes, AG (rs1799971-rs1381376) and AT (rs1799971-rs3778151), were observed as potential protective factors. These emerging findings contribute to the literature on genetic biomarkers of drug dependence and related endophenotypes, and call for replication in independent population.