Sharafshah Alireza, Fazel Hedyeh, Albonaim Ali, Omarmeli Vahid, Rezaei Sajjad, Mirzajani Ebrahim, Ajamian Farzam, Keshavarz Parvaneh
a Master's Student, Cellular and Molecular Research Center , Faculty of Medicine, Guilan University of Medical Sciences , Rasht , Iran.
b Master's Student, Genetic Laboratory, Department of Biology, Faculty of Sciences , University of Guilan , Rasht , Iran.
J Psychoactive Drugs. 2017 Jul-Aug;49(3):242-251. doi: 10.1080/02791072.2017.1290303. Epub 2017 Mar 1.
Genetic association of rs678849 along with neuroimaging and biomarker phenotypes, parallel with the known involvements of the OPRD1 in drug abuse, provided additional support for targeting these receptors as potential therapeutic targets in both neurodegenerative diseases and neuropsychiactric disorders such as Alzheimer's disease. Samples were selected among 202 opium-addicted participants undergoing methadone treatment and 202 healthy controls. Genomic DNA of all subjects was extracted from whole blood samples through a Salting Out procedure. Four variants (rs678849, 2236857, 2236855, and 760589) were genotyped in the studied subjects using ARMS-PCR. The analysis was performed using SNPalyze and SPSS ver.20 software. According to single locus analysis, rs678849 under dominant model (p < 0.001), rs2236857 under recessive model (p = 0.006), and the two variants, rs2236855 and rs760589 under co-dominant model, showed significant contributions between groups (p = 0.001 and p = 0.009, respectively). rs2236855 was associated with the development of libido dysfunction in opium-addicted patients undergoing methadone treatment (p = 0.011). Through haplotype analyses, five haplotypes with frequency of more than 5% displayed significant association with opioid dependence in study participants. In conclusion, the four studied OPRD1 gene variants and their haplotypes can play important roles in susceptibility to opioid dependence.
rs678849与神经影像学和生物标志物表型的遗传关联，与已知的OPRD1在药物滥用中的作用相平行，为将这些受体作为神经退行性疾病和神经精神疾病（如阿尔茨海默病）的潜在治疗靶点提供了额外支持。样本选自202名接受美沙酮治疗的鸦片成瘾参与者和202名健康对照。通过盐析法从全血样本中提取所有受试者的基因组DNA。使用ARMS-PCR对研究对象中的四个变体（rs678849、2236857、2236855和760589）进行基因分型。使用SNPalyze和SPSS 20版软件进行分析。根据单基因座分析，rs678849在显性模型下（p < 0.001）、rs2236857在隐性模型下（p = 0.006），以及rs2236855和rs760589这两个变体在共显性模型下，组间显示出显著差异（分别为p = 0.001和p = 0.009）。rs2236855与接受美沙酮治疗的鸦片成瘾患者性欲功能障碍的发生有关（p = 0.011）。通过单倍型分析，五个频率超过5%的单倍型与研究参与者的阿片类药物依赖显著相关。总之，所研究的四个OPRD1基因变体及其单倍型在阿片类药物依赖易感性中可能起重要作用。
