OPRD1 gene affects disease vulnerability and environmental stress in patients with heroin dependence in Han Chinese
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
Authors: Huang, Chang-Chih; Kuo, Shin-Chang; Yeh, Ta-Chuan; Yeh, Yi-Wei; Chen, Chun-Yen; Liang, Chih-Sung; Tsou, Chang-Chih; Lin, Chun-Long; Ho, Pei-Shen; Huang, San-Yuan
Abstract
Exposure to stress not only increases the vulnerability to heroin dependence (HD) but also provokes relapse. The etiology of HD and the role of life stress remain unclear, but prior studies suggested that both genetic and environmental factors are important. Opioid related genes, including OPRM1, OPRD1, OPRK1, and POMC, are obvious candidates for HD. Therefore, this study was conducted to explore whether the genetic polymorphisms of the candidates could affect vulnerability to HD and response to life stress in patients with HD. Ten polymorphisms of the opioid related genes were analyzed in 801 patients and 530 controls. The Life Event Questionnaire was used to assess the perspective and response to life stress in the past year. The genotype distribution and allelic frequency analyses showed that the minor C allele of rs2234918 in OPRD1 is over-represented in the HD group (P = .006 and P = .002, respectively). This finding was further confirmed by logistic regression analysis, showing that C allele carriers have a 1.42 times greater risk for HD compared to T/T homozygotes. A subgroup of 421 patients and 135 controls were eligible for life stress assessment. Patients with HD have a higher occurrence of negative events (No), negative events score (Ns), and average negative event score (Na) than those of controls (all P < .001), but there was no difference regarding positive recent events between the two groups. Gene-stress assessment in the HD group showed that T/T homozygotes of OPRD1 rs2236857 have more severe stress than C allele carriers (Ns, P = .004 and Na, P = .047). Our results indicate that the OPRD1 gene may not only play a role in the pathogenesis of HD but also affect the response to life stress among patients with HD in our Han Chinese population. Patients with the risk genotype may need additional psychosocial intervention for relapse prevention.
Genetic association analyses and meta-analysis of Dynorphin-Kappa Opioid system potential functional variants with heroin dependence
NEUROSCIENCE LETTERS
Authors: Ji Yuanyuan; Su Rui; Tang Hua; Cui Jingjing; Cuola, Deji; Shi Yuhui; Wei Shuguang
Abstract
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.