Wang Sheng-Chang, Tsou Hsiao-Hui, Chung Ren-Hua, Chang Yao-Sheng, Fang Chiu-Ping, Chen Chia-Hui, Ho Ing-Kang, Kuo Hsiang-Wei, Liu Shu Chih, Shih Yu-Huei, Wu Hsiao-Yu, Huang Bo-Hau, Lin Keh-Ming, Chen Andrew C H, Hsiao Chin-Fu, Liu Yu-Li
From the *Center for Neuropsychiatric Research, and †Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Miaoli County; ‡Center for Drug Abuse and Addiction, China Medical University Hospital; §Graduate Institute of Clinical Medical Science, China Medical University; ∥Department of Pharmacy, China Medical University Hospital, Taichung, Taiwan; ¶Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY; #Division of Clinical Trial Statistics, Institute of Population Health Sciences, National Health Research Institutes, Miaoli County; and**Department of Psychiatry, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
J Clin Psychopharmacol. 2014 Apr;34(2):205-11. doi: 10.1097/JCP.0000000000000082.
Methadone is a synthetic opioid that binds to the κ-opioid receptor with a low affinity. This study tested the hypotheses that the genetic polymorphisms in the κ-opioid receptor 1 (OPRK1) gene region are associated with methadone treatment responses in a Taiwan methadone maintenance treatment (MMT) cohort. Seventeen single nucleotide polymorphisms (SNPs) in OPRK1 were selected and genotyped on DNA of 366 MMT patients. Six SNPs from rs7843965 to rs1051660 (intron 2 to exon 2) were significantly associated with body weight (P < 0.007). A haplotype of 4 SNPs rs7832417-rs16918853-rs702764-rs7817710 (exon 4 to intron 3) was associated with bone or joint aches (P ≤ 0.004) and with the amount of alcohol use (standard drinks per day; global P < 0.0001). The haplotype rs10958350-rs7016778-rs12675595 was associated with gooseflesh skin (global P < 0.0001), yawning (global P = 0.0001), and restlessness (global P < 0.0001) withdrawal symptoms. The findings suggest that genetic polymorphisms in OPRK1 were associated with the body weight, alcohol use, and opioid withdrawal symptoms in MMT patients.
美沙酮是一种合成阿片类药物，它与κ-阿片受体的结合亲和力较低。本研究检验了以下假设：κ-阿片受体1（OPRK1）基因区域的基因多态性与台湾美沙酮维持治疗（MMT）队列中的美沙酮治疗反应相关。选择了OPRK1中的17个单核苷酸多态性（SNP），并对366例MMT患者的DNA进行基因分型。从rs7843965到rs1051660（内含子2到外显子2）的6个SNP与体重显著相关（P < 0.007）。4个SNP rs7832417-rs16918853-rs702764-rs7817710（外显子4到内含子3）的单倍型与骨或关节疼痛（P ≤ 0.004）以及酒精使用量（每天标准饮酒量；总体P < 0.0001）相关。单倍型rs10958350-rs7016778-rs12675595与鸡皮疙瘩皮肤（总体P < 0.0001）、打哈欠（总体P = 0.0001）和烦躁不安（总体P < 0.0001）等戒断症状相关。研究结果表明，OPRK1基因多态性与MMT患者的体重、酒精使用及阿片类药物戒断症状相关。
