Genetic polymorphisms in the opioid receptor mu1 gene are associated with changes in libido and insomnia in methadone maintenance patients

Wang, Sheng-Chang; Tsou, Hsiao-Hui; Chen, Chia‐Hui; Chen, Yuting; Ho, Ing-Kang; Hsiao, Chin‐Fu; Chou, Sun‐Yuan; Lin, Yen-Feng; Fang, Kai-Chi; Huang, Chieh-Liang; Su, Lien-Wen; Fang, Yung-Chun; Liu, Ming-Lun; Wu, Hsiao-Yu; Lin, Keh‐Ming; Liu, Shu Chih; Kuo, Hsin‐Wei; Chiang, I-Chen; Chen, Andrew C. H.; Tian, Jia-Ni; Liu, Yuli

doi:10.1016/j.euroneuro.2012.02.002

Cited by 49 publications

(44 citation statements)

References 45 publications

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“…We also found that those OPRM1 SNPs that were significantly associated with the plasma cotinine concentrations in recessive model were also significantly associated with insomnia side effect in recessive model in our previous report, 35 except SNPs rs1799971 and rs553202. Insomnia is a relatively uncommon side effect in heroin-dependent patients under methadone treatment.…”

Section: Discussionmentioning

confidence: 57%

“…35 Minor allele carriers, who had higher change in libido scores, had higher plasma cotinine concentration than their counter allele in our MMT cohort. Without the involvement of OPRM1 genetic polymorphism, our database did not show a directly significant association between the change in libido score and the plasma cotinine concentration (Kruskal-Wallis test P ¼ 0.701; data not shown).…”

Section: Discussionmentioning

confidence: 94%

“…35 Single locus and haplotype of OPRM1 All 15 selected SNPs were spanning for 63 195 base pairs (bps) across the OPRM1 genetic region with an average distance of 4213 bps OPRM1 is associated with plasma concentration of cotinine The plasma concentration of cotinine was significantly associated with those selected SNPs of OPRM1 using additive model of analyses in allele types (Po0.03 after adjusted with age, gender and body mass index; Table 2), except rs499796. After controlled for multiple testing by the FDR, the results remained statistically significant for the allele types (FDRp0.049), except rs2075572.…”

Section: Clinical Characteristics and Methadone Treatment Outcomementioning

confidence: 99%

“…34 In our previous study, we found that patients with the G allele required higher a methadone dose than those with the A allele. 35 Furthermore, rs1799971 has also been reported to be significantly associated with long-term smoking cessation in both males and females, 36 with nicotine reinforcement in women, and with the brain m-opioid receptor binding potential in smokers. 11,15 However, the results are not consistent.…”

Section: Introductionmentioning

confidence: 99%

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OPRM1 genetic polymorphisms are associated with the plasma nicotine metabolite cotinine concentration in methadone maintenance patients: a cross sectional study

et al. 2012

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Majority of the heroin-dependent patients smoke cigarettes. Although it has been reported that the OPRM1 genetic polymorphism is associated with the brain mu-opioid receptor binding potential in cigarette smokers, there is no direct evidence showing the impact of plasma cotinine, a nicotine metabolite, on treatment responses to methadone maintenance treatment (MMT). In this study, we aimed to test the hypothesis that the genetic polymorphisms in the OPRM1 are associated with the methadone treatment responses and the severity of cigarette smoking directly measured by the plasma concentration of cotinine in a Taiwanese MMT cohort. Fifteen OPRM1 single-nucleotide polymorphisms (SNPs) were selected and genotyped on DNA samples of 366 MMT patients. Plasma concentrations of cotinine were measured by cotinine enzyme-linked immunosorbent assay. The plasma cotinine concentration had positive correlation with concentrations of methadone (P ¼ 0.042) and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenyl-pyrrolidine (P ¼ 0.037). Methadone treatment non-responders, defined by a positive urine morphine test, had a higher plasma concentration of cotinine (P ¼ 0.005), but a lower plasma concentration-todose ratio of both R-and S-methadone (P ¼ 0.001 and 0.012, respectively) than the responders. OPRM1 genetic variants, rs1074287, rs6912029, rs1799971, rs12209447, rs510769, rs3798676, rs553202, rs7748401, rs495491, rs10457090, rs589046, rs3778152 and rs563649, were significantly associated with the plasma concentration of cotinine when using recessive model for genotypes (general linear model (GLM), Po0.038; false discovery rate (FDR)o0.035) and additive model for allele types (GLM, Po0.03; FDRo0.049) in association analyses. The G allele carriers of SNP rs1799971 (A118G) on exon 1 of OPRM1 gene had a lower plasma cotinine concentration than the A allele carriers (GLM, P ¼ 0.029). OPRM1 genetic polymorphisms are associated with the plasma concentration of cotinine in a Taiwanese MMT cohort. Carriers with the major allele of SNP rs1799971 had a higher plasma cotinine concentration.

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Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 94%

Section: Clinical Characteristics and Methadone Treatment Outcomementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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OPRM1 genetic polymorphisms are associated with the plasma nicotine metabolite cotinine concentration in methadone maintenance patients: a cross sectional study

et al. 2012

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“…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). It is highly possible that the OPRM1 affects sleep by acting on different mechanisms in opioid-naive individuals and opioid-dependent patients (Wang et al, 2012;García-García, Drucker-Colín, 1999). At this juncture, it is difficult to explain the differential effects on sleep quality among opioid-naive individuals and opioid-dependent patients with these polymorphisms and further studies are needed.…”

Section: Discussionmentioning

confidence: 99%

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

Zahari

Ibrahim

Musa

et al. 2018

Braz. J. Pharm. Sci.

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Opioidergic system involves in regulation of sleep and wakefulness. It is possible, therefore, that genetic polymorphisms in OPRM1 influence sleep quality. This study investigated the association of OPRM1 polymorphisms with subjective sleep quality among opioid-naive individuals. This cross-sectional observational study involved 161 opioid-naive males (mean age = 27.74 years; range: 18−63 years). Subjective sleep quality was assessed with the translated and validated Malay version of the Pittsburgh Sleep Quality Index (PSQI). DNA was extracted from whole blood and subjected to polymerase chain reaction (PCR)-genotyping for two OPRM1 polymorphisms (118A>G and IVS2+691G>C). Subjects with combined 118A and IVS2+691G alleles (AC haplotype) had significantly lower PSQI scores [mean (SD) = 4.29 (1.76)] compared to those without the haplotype [4.99 (2.50)] (p = 0.004). On the other hand, subjects with combined heterozygous genotype (GC/AG diplotype) had significantly higher PSQI scores compared to those without the diplotype [6.04 (2.48) vs 4.54 (2.22), p = 0.004]. In opioid-naive individuals, AC haplotype and GC/AG diplotype for the 118A>G and IVS2+691G>C polymorphisms of OPRM1 are associated with better and poorer sleep quality, respectively.

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Association between rs1799971 in the mu opioid receptor gene and methadone maintenance treatment response

Xie

Zhuang

et al. 2022

Clinical Laboratory Analysis

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Heroin dependence is an ongoing public health issue worldwide, and methadone maintenance treatment (MMT) is currently an effective substitution therapy for patients with heroin addiction. Methadone, as a synthetic agonist of the mu opioid receptor, can reduce illicit opiate use and improve social rehabilitation. 1,2 There is an obvious difference in individual response to methadone due to large interindividual variability in its pharmacokinetics and pharmacodynamics. [3][4][5][6][7] Optimal personalized medicine for each patient is vital for successful MMT. 8,9 Genetic factors are related to the diversity of individuals in responding to MMT. [10][11][12] Several articles reported that numerous variations in multiple genes are related to modification of the individual MMT response. [13][14][15] Single nucleotide polymorphisms (SNPs) of several genes are significant associations with MMT, such as the genes

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Genetic polymorphisms in the opioid receptor mu1 gene are associated with changes in libido and insomnia in methadone maintenance patients

Cited by 49 publications

References 45 publications

OPRM1 genetic polymorphisms are associated with the plasma nicotine metabolite cotinine concentration in methadone maintenance patients: a cross sectional study

OPRM1 genetic polymorphisms are associated with the plasma nicotine metabolite cotinine concentration in methadone maintenance patients: a cross sectional study

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

Association between rs1799971 in the mu opioid receptor gene and methadone maintenance treatment response

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