title: Genetic polymorphisms in the opioid receptor mu1 gene are associated with changes in libido and insomnia in methadone maintenance patients.
abstract: Methadone, a synthetic racemic opioid that primarily works as a μ-opioid receptor (OPRM1) agonist, is commonly used for the treatment of heroin addiction. Genetic association studies have reported that the OPRM1 gene is involved in the physiology of heroin and alcohol addiction. Our current study is designed to test the hypothesis that genetic polymorphisms in the OPRM1 gene region are associated with methadone dosage, plasma concentrations, treatment responses, adverse reactions and withdrawal symptoms in a methadone maintenance treatment (MMT) cohort from Taiwan. Fifteen OPRM1 single nucleotide polymorphisms (SNPs) were selected and genotyped using DNA samples from 366 MMT patients. The plasma concentrations of methadone and its metabolite were measured by high performance liquid chromatography. The results obtained using dominant model analysis indicate that the OPRM1 SNPs rs1074287, rs6912029, rs12209447, rs510769, rs3798676, rs7748401, rs495491, rs10457090, rs589046, rs3778152, rs563649, and rs2075572 are significantly associated with change-in-libido side effects (adjusted p<0.042). Using recessive model analysis, these SNPs were also found to be significantly associated with insomnia side effects in this cohort (p<0.009). The significance of the insomnia findings was mainly contributed by a subgroup of patients who had a positive urine morphine test (p<0.022), and by individuals who did not use benzodiazepine hypnotics (p<0.034). Our current data thus suggest that genetic polymorphisms in OPRM1 may influence the change-in-libido and insomnia side effects sometimes found in MMT patients.
authors.affiliation: Division of Mental Health and Addiction Medicine, Institute of Population Health Sciences, National Health Research Institutes, Miaoli County, Taiwan.
authors.forename: Sheng-Chang
authors.initials: SC
authors.lastname: Wang
authors.forename: Hsiao-Hui
authors.initials: HH
authors.lastname: Tsou
authors.forename: Chia-Hui
authors.initials: CH
authors.lastname: Chen
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Chen
authors.forename: Ing-Kang
authors.initials: IK
authors.lastname: Ho
authors.forename: Chin-Fu
authors.initials: CF
authors.lastname: Hsiao
authors.forename: Sun-Yuan
authors.initials: SY
authors.lastname: Chou
authors.forename: Yen-Feng
authors.initials: YF
authors.lastname: Lin
authors.forename: Kai-Chi
authors.initials: KC
authors.lastname: Fang
authors.forename: Chieh-Liang
authors.initials: CL
authors.lastname: Huang
authors.forename: Lien-Wen
authors.initials: LW
authors.lastname: Su
authors.forename: Yung-Chun
authors.initials: YC
authors.lastname: Fang
authors.forename: Ming-Lun
authors.initials: ML
authors.lastname: Liu
authors.forename: Hsiao-Yu
authors.initials: HY
authors.lastname: Wu
authors.forename: Keh-Ming
authors.initials: KM
authors.lastname: Lin
authors.forename: Shu Chih
authors.initials: SC
authors.lastname: Liu
authors.forename: Hsiang-Wei
authors.initials: HW
authors.lastname: Kuo
authors.forename: I-Chen
authors.initials: IC
authors.lastname: Chiang
authors.forename: Andrew C H
authors.initials: AC
authors.lastname: Chen
authors.forename: Jia-Ni
authors.initials: JN
authors.lastname: Tian
authors.forename: Yu-Li
authors.initials: YL
authors.lastname: Liu
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001569:Benzodiazepines / Q000627:therapeutic use; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D056726:Genetic Association Studies; D006556:Heroin Dependence / Q000097:blood / Q000188:drug therapy / Q000378:metabolism / Q000652:urine; D006801:Humans; D006993:Hypnotics and Sedatives / Q000627:therapeutic use; D007989:Libido / Q000187:drug effects*; D008297:Male; D008691:Methadone / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D009020:Morphine / Q000633:toxicity / Q000652:urine; D058850:Opiate Substitution Treatment / Q000009:adverse effects; D020641:Polymorphism, Single Nucleotide; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D020018:Sexual Dysfunctions, Psychological / Q000139:chemically induced / Q000453:epidemiology / Q000235:genetics; D007319:Sleep Initiation and Maintenance Disorders / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control; D015813:Substance Abuse Detection; D016320:Substance Abuse Treatment Centers; D013624:Taiwan / Q000453:epidemiology
chemical_list: D000701:Analgesics, Opioid; D006993:Hypnotics and Sedatives; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D001569:Benzodiazepines; D009020:Morphine; D008691:Methadone