Skip to main content
Top
Published in: Pain and Therapy 1/2016

Open Access 01-06-2016 | Original Research

The AC/AG Diplotype for the 118A>G and IVS2 + 691G>C Polymorphisms of OPRM1 Gene is Associated with Sleep Quality Among Opioid-Dependent Patients on Methadone Maintenance Therapy

Authors: Zalina Zahari, Chee Siong Lee, Muslih Abdulkarim Ibrahim, Nurfadhlina Musa, Mohd Azhar Mohd Yasin, Yeong Yeh Lee, Soo Choon Tan, Nasir Mohamad, Rusli Ismail

Published in: Pain and Therapy | Issue 1/2016

Login to get access

Abstract

Introduction

Methadone is a full agonist of the opioid receptor mu 1 which is encoded by the OPRM1 gene. Sleep disorders were frequently reported by opioid-dependent patients during methadone maintenance therapy (MMT). It is possible, therefore, that genetic polymorphisms in OPRM1 influence sleep quality among patients on MMT. This study investigated the association of OPRM1 polymorphisms with sleep quality among opioid-dependent patients on MMT.

Methods

The sleep quality of 165 male opioid-dependent patients receiving MMT was evaluated using the Pittsburgh Sleep Quality Index (PSQI). DNA was extracted from whole blood and subjected to polymerase chain reaction (PCR) genotyping.

Results

Patients with IVS2 + 691 CC genotype had higher PSQI scores [mean (SD) = 5.73 (2.89)] compared to those without the IVS2 + 691 CC genotype (IVS2 + 691 GG/GC genotype) [4.92 (2.31)], but the difference did not reach statistical significance (p = 0.081). Patients with combined 118 AA genotype and IVS2 + 691 GC genotype (AC/AG diplotype) had significantly lower PSQI scores [mean (SD) = 4.25 (2.27)] compared to those without the diplotype [5.68 (2.77)] (p = 0.018).

Conclusion

Our study indicates that the AC/AG diplotype for the 118A>G and IVS2 + 691G>C polymorphisms of OPRM1 gene is associated with better sleep quality among males with opioid dependence on MMT.
Literature
1.
go back to reference Hsu W-Y, Chiu N-Y, Liu J-T, et al. Sleep quality in heroin addicts under methadone maintenance treatment. Acta Neuropsychiatr. 2012;24(6):356–60.CrossRefPubMed Hsu W-Y, Chiu N-Y, Liu J-T, et al. Sleep quality in heroin addicts under methadone maintenance treatment. Acta Neuropsychiatr. 2012;24(6):356–60.CrossRefPubMed
2.
go back to reference Liao Y, Tang J, Liu T, Chen X, Luo T, Hao W. Sleeping problems among Chinese heroin-dependent individuals. Am J Drug Alcohol Abuse. 2011;37(3):179–83.CrossRefPubMed Liao Y, Tang J, Liu T, Chen X, Luo T, Hao W. Sleeping problems among Chinese heroin-dependent individuals. Am J Drug Alcohol Abuse. 2011;37(3):179–83.CrossRefPubMed
3.
go back to reference Peles E, Schreiber S, Adelson M. Variables associated with perceived sleep disorders in methadone maintenance treatment (MMT) patients. Drug Alcohol Depend. 2006;82(2):103–10.CrossRefPubMed Peles E, Schreiber S, Adelson M. Variables associated with perceived sleep disorders in methadone maintenance treatment (MMT) patients. Drug Alcohol Depend. 2006;82(2):103–10.CrossRefPubMed
4.
go back to reference Peles E, Schreiber S, Adelson M. Documented poor sleep among methadone-maintained patients is associated with chronic pain and benzodiazepine abuse, but not with methadone dose. Eur Neuropsychopharmacol. 2009;19(8):581–8.CrossRefPubMed Peles E, Schreiber S, Adelson M. Documented poor sleep among methadone-maintained patients is associated with chronic pain and benzodiazepine abuse, but not with methadone dose. Eur Neuropsychopharmacol. 2009;19(8):581–8.CrossRefPubMed
5.
go back to reference Pud D, Zlotnick C, Lawental E. Pain depression and sleep disorders among methadone maintenance treatment patients. Addict Behav. 2012;37(11):1205–10.CrossRefPubMed Pud D, Zlotnick C, Lawental E. Pain depression and sleep disorders among methadone maintenance treatment patients. Addict Behav. 2012;37(11):1205–10.CrossRefPubMed
6.
go back to reference Stein MD, Herman DS, Bishop S, et al. Sleep disturbances among methadone maintained patients. J Subst Abuse Treat. 2004;26(3):175–80.CrossRefPubMed Stein MD, Herman DS, Bishop S, et al. Sleep disturbances among methadone maintained patients. J Subst Abuse Treat. 2004;26(3):175–80.CrossRefPubMed
7.
go back to reference Wang D, Teichtahl H, Drummer O, et al. Central sleep apnea in stable methadone maintenance treatment patients. Chest. 2005;128(3):1348–56.CrossRefPubMed Wang D, Teichtahl H, Drummer O, et al. Central sleep apnea in stable methadone maintenance treatment patients. Chest. 2005;128(3):1348–56.CrossRefPubMed
8.
go back to reference Wang D, Teichtahl H, Goodman C, Drummer O, Grunstein RR, Kronborg I. Subjective daytime sleepiness and daytime function in patients on stable methadone maintenance treatment: possible mechanisms. J Clin Sleep Med. 2008;4(6):557–62.PubMedPubMedCentral Wang D, Teichtahl H, Goodman C, Drummer O, Grunstein RR, Kronborg I. Subjective daytime sleepiness and daytime function in patients on stable methadone maintenance treatment: possible mechanisms. J Clin Sleep Med. 2008;4(6):557–62.PubMedPubMedCentral
9.
go back to reference Beswick T, Best D, Rees S, Bearn J, Gossop M, Strang J. Major disruptions of sleep during treatment of the opiate withdrawal syndrome: differences between methadone and lofexidine detoxification treatments. Addict Biol. 2003;8(1):49–57.CrossRefPubMed Beswick T, Best D, Rees S, Bearn J, Gossop M, Strang J. Major disruptions of sleep during treatment of the opiate withdrawal syndrome: differences between methadone and lofexidine detoxification treatments. Addict Biol. 2003;8(1):49–57.CrossRefPubMed
10.
go back to reference Gossop M, Bradley B. Insomnia among addicts during supervised withdrawal from opiates: a comparison of oral methadone and electrostimulation. Drug Alcohol Depend. 1984;13(2):191–8.CrossRefPubMed Gossop M, Bradley B. Insomnia among addicts during supervised withdrawal from opiates: a comparison of oral methadone and electrostimulation. Drug Alcohol Depend. 1984;13(2):191–8.CrossRefPubMed
11.
go back to reference Oyefeso A, Sedgwick P, Ghodse H. Subjective sleep-wake parameters in treatment-seeking opiate addicts. Drug Alcohol Depend. 1997;48(1):9–16.CrossRefPubMed Oyefeso A, Sedgwick P, Ghodse H. Subjective sleep-wake parameters in treatment-seeking opiate addicts. Drug Alcohol Depend. 1997;48(1):9–16.CrossRefPubMed
12.
go back to reference Staedt J, Wassmuth F, Stoppe G, et al. Effects of chronic treatment with methadone and naltrexone on sleep in addicts. Eur Arch Psychiatry Clin Neurosci. 1996;246(6):305–9.CrossRefPubMed Staedt J, Wassmuth F, Stoppe G, et al. Effects of chronic treatment with methadone and naltrexone on sleep in addicts. Eur Arch Psychiatry Clin Neurosci. 1996;246(6):305–9.CrossRefPubMed
14.
go back to reference Nelson AM, Battersby AS, Baghdoyan HA, Lydic R. Opioid-induced decreases in rat brain adenosine levels are reversed by inhibiting adenosine deaminase. Anesthesiology. 2009;111(6):1327–33.CrossRefPubMedPubMedCentral Nelson AM, Battersby AS, Baghdoyan HA, Lydic R. Opioid-induced decreases in rat brain adenosine levels are reversed by inhibiting adenosine deaminase. Anesthesiology. 2009;111(6):1327–33.CrossRefPubMedPubMedCentral
15.
go back to reference Klepstad P, Rakvag TT, Kaasa S, et al. The 118 A>G polymorphism in the human mu-opioid receptor gene may increase morphine requirements in patients with pain caused by malignant disease. Acta Anaesthesiol Scand. 2004;48(10):1232–9.CrossRefPubMed Klepstad P, Rakvag TT, Kaasa S, et al. The 118 A>G polymorphism in the human mu-opioid receptor gene may increase morphine requirements in patients with pain caused by malignant disease. Acta Anaesthesiol Scand. 2004;48(10):1232–9.CrossRefPubMed
16.
go back to reference Befort K, Filliol D, Decaillot FM, Gaveriaux-Ruff C, Hoehe MR, Kieffer BL. A single nucleotide polymorphic mutation in the human mu-opioid receptor severely impairs receptor signaling. J Biol Chem. 2001;276(5):3130–7.CrossRefPubMed Befort K, Filliol D, Decaillot FM, Gaveriaux-Ruff C, Hoehe MR, Kieffer BL. A single nucleotide polymorphic mutation in the human mu-opioid receptor severely impairs receptor signaling. J Biol Chem. 2001;276(5):3130–7.CrossRefPubMed
17.
go back to reference Ravindranathan A, Joslyn G, Robertson M, Schuckit MA, Whistler JL, White RL. Functional characterization of human variants of the mu-opioid receptor gene. Proc Natl Acad Sci USA. 2009;106(26):10811–6.CrossRefPubMedPubMedCentral Ravindranathan A, Joslyn G, Robertson M, Schuckit MA, Whistler JL, White RL. Functional characterization of human variants of the mu-opioid receptor gene. Proc Natl Acad Sci USA. 2009;106(26):10811–6.CrossRefPubMedPubMedCentral
18.
go back to reference Huang P, Chen C, Mague SD, Blendy JA, Liu-Chen LY. A common single nucleotide polymorphism A118G of the mu opioid receptor alters its N-glycosylation and protein stability. Biochem J. 2012;441(1):379–86.CrossRefPubMedPubMedCentral Huang P, Chen C, Mague SD, Blendy JA, Liu-Chen LY. A common single nucleotide polymorphism A118G of the mu opioid receptor alters its N-glycosylation and protein stability. Biochem J. 2012;441(1):379–86.CrossRefPubMedPubMedCentral
19.
go back to reference Xin L, Wang ZJ. Bioinformatic analysis of the human mu opioid receptor (OPRM1) splice and polymorphic variants. AAPS PharmSci. 2002;4(4):E23.CrossRefPubMed Xin L, Wang ZJ. Bioinformatic analysis of the human mu opioid receptor (OPRM1) splice and polymorphic variants. AAPS PharmSci. 2002;4(4):E23.CrossRefPubMed
20.
go back to reference Hoehe MR, Kopke K, Wendel B, et al. Sequence variability and candidate gene analysis in complex disease: association of mu opioid receptor gene variation with substance dependence. Hum Mol Genet. 2000;9(19):2895–908.CrossRefPubMed Hoehe MR, Kopke K, Wendel B, et al. Sequence variability and candidate gene analysis in complex disease: association of mu opioid receptor gene variation with substance dependence. Hum Mol Genet. 2000;9(19):2895–908.CrossRefPubMed
21.
go back to reference Lotsch J, Geisslinger G. Relevance of frequent mu-opioid receptor polymorphisms for opioid activity in healthy volunteers. Pharmacogenomics J. 2006;6(3):200–10.CrossRefPubMed Lotsch J, Geisslinger G. Relevance of frequent mu-opioid receptor polymorphisms for opioid activity in healthy volunteers. Pharmacogenomics J. 2006;6(3):200–10.CrossRefPubMed
22.
go back to reference Wendel B, Hoehe MR. The human mu opioid receptor gene: 5′ regulatory and intronic sequences. J Mol Med (Berl). 1998;76(7):525–32.CrossRefPubMed Wendel B, Hoehe MR. The human mu opioid receptor gene: 5′ regulatory and intronic sequences. J Mol Med (Berl). 1998;76(7):525–32.CrossRefPubMed
23.
go back to reference Compton P, Geschwind DH, Alarcon M. Association between human mu-opioid receptor gene polymorphism, pain tolerance, and opioid addiction. Am J Med Genet B Neuropsychiatr Genet. 2003;121B(1):76–82.CrossRefPubMed Compton P, Geschwind DH, Alarcon M. Association between human mu-opioid receptor gene polymorphism, pain tolerance, and opioid addiction. Am J Med Genet B Neuropsychiatr Genet. 2003;121B(1):76–82.CrossRefPubMed
24.
go back to reference Wang SC, Tsou HH, Chen CH, et al. Genetic polymorphisms in the opioid receptor mu1 gene are associated with changes in libido and insomnia in methadone maintenance patients. Eur Neuropsychopharmacol. 2012;22(10):695–703.CrossRefPubMed Wang SC, Tsou HH, Chen CH, et al. Genetic polymorphisms in the opioid receptor mu1 gene are associated with changes in libido and insomnia in methadone maintenance patients. Eur Neuropsychopharmacol. 2012;22(10):695–703.CrossRefPubMed
25.
go back to reference Fonseca F, Gratacos M, Escaramis G, et al. Response to methadone maintenance treatment is associated with the MYOCD and GRM6 genes. Mol Diagn Ther. 2010;14(3):171–8.CrossRefPubMed Fonseca F, Gratacos M, Escaramis G, et al. Response to methadone maintenance treatment is associated with the MYOCD and GRM6 genes. Mol Diagn Ther. 2010;14(3):171–8.CrossRefPubMed
26.
go back to reference Bunten H, Liang WJ, Pounder DJ, Seneviratne C, Osselton D. Interindividual variability in the prevalence of OPRM1 and CYP2B6 gene variations may identify drug-susceptible populations. J Anal Toxicol. 2011;35(7):431–7.CrossRefPubMed Bunten H, Liang WJ, Pounder DJ, Seneviratne C, Osselton D. Interindividual variability in the prevalence of OPRM1 and CYP2B6 gene variations may identify drug-susceptible populations. J Anal Toxicol. 2011;35(7):431–7.CrossRefPubMed
27.
go back to reference Bunten H, Liang WJ, Pounder DJ, Seneviratne C, Osselton D. OPRM1 and CYP2B6 gene variants as risk factors in methadone-related deaths. Clin Pharmacol Ther. 2010;88(3):383–9.CrossRefPubMed Bunten H, Liang WJ, Pounder DJ, Seneviratne C, Osselton D. OPRM1 and CYP2B6 gene variants as risk factors in methadone-related deaths. Clin Pharmacol Ther. 2010;88(3):383–9.CrossRefPubMed
28.
go back to reference Zahari Z, Lee CS, Ibrahim MA, et al. The opposing roles of IVS2 + 691 CC genotype and AC/AG diplotype of 118A>G and IVS2 + 691G>C of OPRM1 polymorphisms in cold pain tolerance among opioid-dependent Malay males on methadone therapy. Pain Ther. 2015;4(2):179–96.CrossRefPubMedPubMedCentral Zahari Z, Lee CS, Ibrahim MA, et al. The opposing roles of IVS2 + 691 CC genotype and AC/AG diplotype of 118A>G and IVS2 + 691G>C of OPRM1 polymorphisms in cold pain tolerance among opioid-dependent Malay males on methadone therapy. Pain Ther. 2015;4(2):179–96.CrossRefPubMedPubMedCentral
29.
go back to reference American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994.
30.
go back to reference Manan MM, Ali SM, Khan MA, Jafarian S, Hameed MA. Review on the demographic and social impact of methadone-medication therapy on Malaysian patients. Pak J Pharm Sci. 2013;26(4):841–6.PubMed Manan MM, Ali SM, Khan MA, Jafarian S, Hameed MA. Review on the demographic and social impact of methadone-medication therapy on Malaysian patients. Pak J Pharm Sci. 2013;26(4):841–6.PubMed
31.
go back to reference Charpentier A, Bisac S, Poirot I, Vignau J, Cottencin O. Sleep quality and apnea in stable methadone maintenance treatment. Subst Use Misuse. 2010;45(9):1431–4.CrossRefPubMed Charpentier A, Bisac S, Poirot I, Vignau J, Cottencin O. Sleep quality and apnea in stable methadone maintenance treatment. Subst Use Misuse. 2010;45(9):1431–4.CrossRefPubMed
32.
go back to reference Kurth ME, Sharkey KM, Millman RP, Corso RP, Stein MD. Insomnia among methadone-maintained individuals: the feasibility of collecting home polysomnographic recordings. J Addict Dis. 2009;28(3):219–25.CrossRefPubMedPubMedCentral Kurth ME, Sharkey KM, Millman RP, Corso RP, Stein MD. Insomnia among methadone-maintained individuals: the feasibility of collecting home polysomnographic recordings. J Addict Dis. 2009;28(3):219–25.CrossRefPubMedPubMedCentral
33.
go back to reference Peles E, Schreiber S, Hamburger RB, Adelson M. No change of sleep after 6 and 12 months of methadone maintenance treatment. J Addict Med. 2011;5(2):141–7.CrossRefPubMed Peles E, Schreiber S, Hamburger RB, Adelson M. No change of sleep after 6 and 12 months of methadone maintenance treatment. J Addict Med. 2011;5(2):141–7.CrossRefPubMed
34.
go back to reference Sharkey KM, Kurth ME, Anderson BJ, Corso RP, Millman RP, Stein MD. Obstructive sleep apnea is more common than central sleep apnea in methadone maintenance patients with subjective sleep complaints. Drug Alcohol Depend. 2010;108(1–2):77–83.CrossRefPubMedPubMedCentral Sharkey KM, Kurth ME, Anderson BJ, Corso RP, Millman RP, Stein MD. Obstructive sleep apnea is more common than central sleep apnea in methadone maintenance patients with subjective sleep complaints. Drug Alcohol Depend. 2010;108(1–2):77–83.CrossRefPubMedPubMedCentral
35.
go back to reference Sharkey KM, Kurth ME, Anderson BJ, Corso RP, Millman RP, Stein MD. Assessing sleep in opioid dependence: a comparison of subjective ratings, sleep diaries, and home polysomnography in methadone maintenance patients. Drug Alcohol Depend. 2011;113(2–3):245–8.CrossRefPubMed Sharkey KM, Kurth ME, Anderson BJ, Corso RP, Millman RP, Stein MD. Assessing sleep in opioid dependence: a comparison of subjective ratings, sleep diaries, and home polysomnography in methadone maintenance patients. Drug Alcohol Depend. 2011;113(2–3):245–8.CrossRefPubMed
36.
go back to reference Sharkey KM, Kurth ME, Corso RP, Brower KJ, Millman RP, Stein MD. Home polysomnography in methadone maintenance patients with subjective sleep complaints. Am J Drug Alcohol Abuse. 2009;35(3):178–82.CrossRefPubMedPubMedCentral Sharkey KM, Kurth ME, Corso RP, Brower KJ, Millman RP, Stein MD. Home polysomnography in methadone maintenance patients with subjective sleep complaints. Am J Drug Alcohol Abuse. 2009;35(3):178–82.CrossRefPubMedPubMedCentral
37.
go back to reference Stein MD, Kurth ME, Sharkey KM, Anderson BJ, Corso RP, Millman RP. Trazodone for sleep disturbance during methadone maintenance: a double-blind, placebo-controlled trial. Drug Alcohol Depend. 2012;120(1–3):65–73.CrossRefPubMed Stein MD, Kurth ME, Sharkey KM, Anderson BJ, Corso RP, Millman RP. Trazodone for sleep disturbance during methadone maintenance: a double-blind, placebo-controlled trial. Drug Alcohol Depend. 2012;120(1–3):65–73.CrossRefPubMed
38.
go back to reference Zahari Z, Lee CS, Tan SC, Mohamad N, Lee YY, Ismail R. Relationship between cold pressor pain-sensitivity and sleep quality in opioid-dependent males on methadone treatment. PeerJ. 2015;3:e839.CrossRefPubMedPubMedCentral Zahari Z, Lee CS, Tan SC, Mohamad N, Lee YY, Ismail R. Relationship between cold pressor pain-sensitivity and sleep quality in opioid-dependent males on methadone treatment. PeerJ. 2015;3:e839.CrossRefPubMedPubMedCentral
39.
go back to reference Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989;28(2):193–213.CrossRefPubMed Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989;28(2):193–213.CrossRefPubMed
40.
go back to reference Mohamed Nazar NI. Therapeutic drug monitoring in methadone maintenance therapy (MMT): an evaluation of genetic factors influencing clinical outcomes and serum concentrations of methadone: Ph.D. Thesis, Universiti Sains Malaysia; 2013. Mohamed Nazar NI. Therapeutic drug monitoring in methadone maintenance therapy (MMT): an evaluation of genetic factors influencing clinical outcomes and serum concentrations of methadone: Ph.D. Thesis, Universiti Sains Malaysia; 2013.
41.
42.
go back to reference Ding S, Chen B, Zheng Y, Lu Q, Liu L, Zhuge QC. Association study of OPRM1 polymorphisms with schizophrenia in Han Chinese population. BMC Psychiatry. 2013;13:107.CrossRefPubMedPubMedCentral Ding S, Chen B, Zheng Y, Lu Q, Liu L, Zhuge QC. Association study of OPRM1 polymorphisms with schizophrenia in Han Chinese population. BMC Psychiatry. 2013;13:107.CrossRefPubMedPubMedCentral
43.
go back to reference Hayashida M, Nagashima M, Satoh Y, et al. Analgesic requirements after major abdominal surgery are associated with OPRM1 gene polymorphism genotype and haplotype. Pharmacogenomics. 2008;9(11):1605–16.CrossRefPubMed Hayashida M, Nagashima M, Satoh Y, et al. Analgesic requirements after major abdominal surgery are associated with OPRM1 gene polymorphism genotype and haplotype. Pharmacogenomics. 2008;9(11):1605–16.CrossRefPubMed
44.
go back to reference Mahfoud Y, Talih F, Streem D, Budur K. Sleep disorders in substance abusers: how common are they? Psychiatry (Edgmont). 2009;6(9):38–42.PubMedPubMedCentral Mahfoud Y, Talih F, Streem D, Budur K. Sleep disorders in substance abusers: how common are they? Psychiatry (Edgmont). 2009;6(9):38–42.PubMedPubMedCentral
Metadata
Title
The AC/AG Diplotype for the 118A>G and IVS2 + 691G>C Polymorphisms of OPRM1 Gene is Associated with Sleep Quality Among Opioid-Dependent Patients on Methadone Maintenance Therapy
Authors
Zalina Zahari
Chee Siong Lee
Muslih Abdulkarim Ibrahim
Nurfadhlina Musa
Mohd Azhar Mohd Yasin
Yeong Yeh Lee
Soo Choon Tan
Nasir Mohamad
Rusli Ismail
Publication date
01-06-2016
Publisher
Springer Healthcare
Published in
Pain and Therapy / Issue 1/2016
Print ISSN: 2193-8237
Electronic ISSN: 2193-651X
DOI
https://doi.org/10.1007/s40122-016-0044-3

Other articles of this Issue 1/2016

Pain and Therapy 1/2016 Go to the issue