title: The association of genetic polymorphisms in the κ-opioid receptor 1 gene with body weight, alcohol use, and withdrawal symptoms in patients with methadone maintenance.
abstract: 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.
authors: 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.
authors: Sheng-Chang
authors: SC
authors: Wang
authors: Hsiao-Hui
authors: HH
authors: Tsou
authors: Ren-Hua
authors: RH
authors: Chung
authors: Yao-Sheng
authors: YS
authors: Chang
authors: Chiu-Ping
authors: CP
authors: Fang
authors: Chia-Hui
authors: CH
authors: Chen
authors: Ing-Kang
authors: IK
authors: Ho
authors: Hsiang-Wei
authors: HW
authors: Kuo
authors: Shu Chih
authors: SC
authors: Liu
authors: Yu-Huei
authors: YH
authors: Shih
authors: Hsiao-Yu
authors: HY
authors: Wu
authors: Bo-Hau
authors: BH
authors: Huang
authors: Keh-Ming
authors: KM
authors: Lin
authors: Andrew C H
authors: AC
authors: Chen
authors: Chin-Fu
authors: CF
authors: Hsiao
authors: Yu-Li
authors: YL
authors: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D000428:Alcohol Drinking / Q000235:genetics*; D001835:Body Weight / Q000235:genetics*; D056726:Genetic Association Studies; D006239:Haplotypes; D006556:Heroin Dependence / Q000188:drug therapy; D006801:Humans; D008691:Methadone / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D058850:Opiate Substitution Treatment / Q000009:adverse effects*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017473:Receptors, Opioid, kappa / Q000235:genetics*; D013375:Substance Withdrawal Syndrome / Q000235:genetics*; D013624:Taiwan; D055815:Young Adult
chemical_list: C515653:OPRK1 protein, human; D017473:Receptors, Opioid, kappa; D008691:Methadone