Jabeen Shagufta, Pinsonneault Julia K, Sadee Wolfgang, Lee Sung-Ha, Zafar Muhammad Mobeen, Raja Muhammad Saqlain, Raja Ghazala Kaukab
University Institute of Biochemistry and Biotechnology, Pir Mehr Ali Shah Arid Agriculture University Rawalpindi, Rawalpindi, Pakistan.
Center for Pharmacogenomics, College of Medicine, The Ohio State University, Columbus, Ohio.
Ann Hum Genet. 2019 Sep;83(5):367-372. doi: 10.1111/ahg.12322. Epub 2019 Apr 26.
The dopamine D2 receptor encoded by DRD2 has been implicated in multiple psychiatric disorders, mediated at least in part by two intronic variants affecting mRNA splicing, rs1076560 and rs2283265, and a less frequent enhancer variant, rs12364283, which increases DRD2 mRNA expression. This study tests whether these functionally validated variants confer susceptibility toward heroin addiction in a Pakistani population. A total of 540 heroin addicts and 467 healthy controls were genotyped, basic allele and genotype tests were performed. Neither rs1076560 nor rs2283265 significantly associated with heroin addiction. The enhancer rs12364283 occurs more frequently in heroin-dependent cases than controls (MAF 13% vs. 7%, respectively), revealing significant association with heroin addiction (p = 3.0E-06, OR 2.1). This study identifies rs12364283 of DRD2 as a potential risk factor for heroin addiction in the Pakistani study population. This enhancer variant had been shown to increase DRD2 mRNA expression, a possible factor in increased vulnerability to heroin addiction. Further studies are needed to validate this association of rs12364283.
由DRD2编码的多巴胺D2受体与多种精神疾病有关，至少部分是由影响mRNA剪接的两个内含子变体rs1076560和rs2283265以及一个较罕见的增强子变体rs12364283介导的，该增强子变体可增加DRD2 mRNA的表达。本研究测试了这些经过功能验证的变体是否会使巴基斯坦人群对海洛因成瘾易感。对总共540名海洛因成瘾者和467名健康对照进行了基因分型，并进行了基本等位基因和基因型检测。rs1076560和rs2283265均与海洛因成瘾无显著关联。增强子rs12364283在海洛因依赖病例中的出现频率高于对照组（分别为MAF 13%和7%），显示出与海洛因成瘾有显著关联（p = 3.0E - 06，OR 2.1）。本研究确定DRD2的rs12364283是巴基斯坦研究人群中海洛因成瘾的潜在风险因素。这种增强子变体已被证明可增加DRD2 mRNA的表达，这可能是海洛因成瘾易感性增加的一个因素。需要进一步研究来验证rs12364283的这种关联。
