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

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.

Sleep quality and OPRM1 polymorphisms: a cross-sectional study among opioid-naive individuals

“…It has been previously demonstrated that the AC/ AG diplotype for the 118A>G and IVS2+691G>C polymorphisms of OPRM1 is associated with better sleep quality among opioid-dependent patients on MMT (Zahari et al, 2016a). However, in opioid-naive individuals, no significant difference of the mean PSQI scores was observed between subjects with the AC/AG diplotype and those without this diplotype (p = 0.368).…”

“…Allele-specific multiplex polymerase chain reaction (PCR) was used to detect OPRM1 polymorphisms [118A>G (dbSNP rs1799971) and IVS2+691G>C (dbSNP rs2075572)] (Mohamed Nazar, 2013; Zahari et al, 2015;Zahari et al, 2016b, Zahari et al, 2016a. All reactions were performed on the Applied Biosystems  Veriti  96-Well Thermal Cycler (Applied Biosystems, USA).…”

Influence of DRD2 polymorphisms on the clinical outcomes of opioiddependent patients on methadone maintenance therapy

“…Concerning genetic factors for sleep disturbance–related side effects of opioids, thus far, only two studies have been conducted among opioid-addicted individuals during methadone treatment. In both studies (i.e., by Wang et al [ 13 ] and Zahari et al [ 11 ]), the OPRM1 polymorphisms have been shown to be associated with methadone-related sleep problems. Wang et al [ 13 ] reported a significant association of OPRM1 polymorphisms with insomnia side effects in a Taiwanese MMT cohort.…”

“…We have reported detailed methods of this study sample previously. [ 1 5 6 7 8 9 10 11 12 , 32 32 34 ] Data used in this study were collected as part of the study to evaluate the application of personalized methadone therapy among patients on MMT. In this cross-sectional study, a total of 148 subjects were recruited from 11 outpatient methadone clinics in Kelantan, Malaysia between March and October 2013.…”

“…Attention has been directed to the genetic factors that might influence treatment outcomes of MMT. [ 9 10 11 12 13 14 15 16 17 18 19 ] Variation in addiction-related genes (such as dopamine receptor D2 gene, DRD2 ) due to polymorphisms in the genetic sequence may explain interindividual differences in clinical outcomes of patients on MMT. [ 9 10 11 12 13 14 15 16 17 18 19 ]…”