Dataset Information

GRK5 Is Associated with the Regulation of Methadone Dosage in Heroin Dependence.

ABSTRACT: Background:There is no countable biomarker for opioid dependence treatment responses thus far. In this study, we recruited Taiwanese methadone maintenance treatment patients to search for genes involving the regulatory mechanisms of methadone dose by genome-wide association analyses. Methods:A total of 344 Taiwanese methadone maintenance treatment patients were included in a genome-wide association study. The involvement of GRK5 in opioid dependence was then further confirmed by gene expression study on lymphoblastoid cell lines derived from 3 independent age- and gender-matched groups: methadone maintenance treatment patients, medication-free former heroin abusers, and normal controls. Results:The results indicated that GRK5, the gene encoding an enzyme related to ?-opioid receptor desensitization, is associated with methadone dose by additive model of gene-based association analysis (P=6.76×10-5). We found that 6 of the 55 single nucleotide polymorphisms from the genome-wide genotype platform and 2 single nucleotide polymorphisms from the 29 additionally selected single nucleotide polymorphisms were significantly associated with methadone maintenance dose in both genotype and allele type (P ? .006), especially in patients who tested negative in the urine morphine test. The levels of GRK5 gene expression were similar between methadone maintenance treatment patients and medication-free former heroin abusers. However, the normal controls showed a significantly lower level of GRK5 gene expression than the other groups (P=.019). Conclusions:The results suggested an important role for GRK5 in the regulatory mechanisms of methadone dose and course of heroin dependence.

SUBMITTER: Wang SC

PROVIDER: S-EPMC6165957 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

GRK5 Is Associated with the Regulation of Methadone Dosage in Heroin Dependence.

Wang Sheng-Chang SC Chung Ren-Hua RH Kuo Hsiang-Wei HW Liu Tung-Hsia TH Fang Chiu-Ping CP Liu Shu Chih SC Liu Chia-Chen CC Tsou Hsiao-Hui HH Chen Andrew C H ACH Liu Yu-Li YL

The international journal of neuropsychopharmacology 20181001 10

<h4>Background</h4>There is no countable biomarker for opioid dependence treatment responses thus far. In this study, we recruited Taiwanese methadone maintenance treatment patients to search for genes involving the regulatory mechanisms of methadone dose by genome-wide association analyses.<h4>Methods</h4>A total of 344 Taiwanese methadone maintenance treatment patients were included in a genome-wide association study. The involvement of GRK5 in opioid dependence was then further confirmed by g ...[more]

PMID: 30060048

Similar Datasets

Project description:Background:In western countries, there is a negative association between religious belief and suicide risk, while in China this association is positive. Nevertheless, few data are available on the association between one specific type of religion and suicide risk, which might be different from the overall positive religion-suicide association in China. This study examined the association between Buddhist belief and suicide risk in Chinese persons receiving methadone maintenance therapy (MMT) for heroin dependence. Methods:In total, 61 Buddhist believers and 425 age, gender, and clinic frequency-matched non-religious believers were selected from a sample of patients with heroin dependence treated in three MMT clinics in Wuhan, China. The suicidality module of the Chinese version of the Mini-international Neuropsychiatric Interview 5.0 was used to assess current suicide risk. Patients' demographic and clinical characteristics were also collected. Multiple ordinary logistic regression was used to analyze the association between Buddhist belief and current suicide risk, controlling for the confounding effects of demographic and clinical factors. Results:In Chinese patients receiving MMT for heroin dependence, Buddhist believers had significantly higher levels of current suicide risk than non-religious believers (low: 45.9% vs. 24.7%, medium: 4.9% vs. 3.5%, high: 19.7% vs. 12.5%, P < 0.001). After adjusting for demographic and clinical covariates (including depressive symptoms), Buddhist belief was still significantly associated with an increase in the level of current suicide risk (OR: 2.98, P < 0.001). Conclusion:Buddhist belief is significantly associated with elevated current suicide risk in Chinese patients receiving MMT for heroin independence. In Chinese MMT clinics, patients with Buddhist belief may have a high current suicide risk and a timely psychiatric assessment and crisis intervention (when necessary) should be provided to these patients.

Project description:Objective: To explore the association between methadone dosage, plasma drug concentration, SNPs of μ-opioid receptor gene (OPRM1), ATP-binding cassette subfamily B member 1 gene (ABCB1), and methadone maintenance treatment (MMT) response. Method: A total of 240 Chinese Han participants receiving MMT were recruited from Shanghai. Nine single nucleotide polymorphisms (SNPs) of the OPRM1 gene and three SNPs of the ABCB1 gene were genotyped, plasma methadone concentration was detected, and a morphine urine test was taken from all subjects. Results: Methadone dosage, plasma methadone concentration, and negative rate of morphine urine test of retention participants were significantly higher, although the addiction severity index (ASI) was not significantly different between the two groups. A allele and AA genotype carriers of rs562859 (OPRM1 gene) had better compliance of MMT, and AA genotype carriers had a higher negative rate of morphine urine test. However, the difference was not significant after adjusting influence factors (age, sex, and methadone dosage). GG genotype carriers of rs3192723 (OPRM1 gene) had a significantly lower negative rate of morphine urine test, and the difference was still significant after adjusting influence factors. Logistic regression analysis showed that methadone-free trough concentration (OR = 0.910, p = 0.023) and AA genotype of rs526859 (OR = 0.580, p = 0.037) were associated with better compliance of MMT. After Bonferroni correction, only free trough concentration of methadone was negatively correlated with MMT compliance. The SNPs rs6912029 (OR = 0.021, p = 0.066) and rs6902403 (OR = 0.910, p = 0.007) of the OPRM1 gene, age at first use (OR = 1.118, p = 0.005), and average methadone dosage (OR = 1.033, p = 0.045) were associated with MMT effect. After Bonferroni correction, average methadone dosage was no longer correlated with MMT effect. Conclusion: Dosage of methadone, plasma methadone concentration, several SNPs (rs3192723, rs6912029, rs6902403) of the OPRM1 gene, and age of first drug use were associated with better MMT outcomes.

Project description:Methadone maintenance treatment (MMT) is commonly used for controlling opioid dependence, preventing withdrawal symptoms, and improving the quality of life of heroin-dependent patients. A steady-state plasma concentration of methadone enantiomers, a measure of methadone metabolism, is an index of treatment response and efficacy of MMT. Although the methadone metabolism pathway has been partially revealed, no genome-wide pharmacogenomic study has been performed to identify genetic determinants and characterize genetic mechanisms for the plasma concentrations of methadone R- and S-enantiomers. This study was the first genome-wide pharmacogenomic study to identify genes associated with the plasma concentrations of methadone R- and S-enantiomers and their respective metabolites in a methadone maintenance cohort. After data quality control was ensured, a dataset of 344 heroin-dependent patients in the Han Chinese population of Taiwan who underwent MMT was analyzed. Genome-wide single-locus and haplotype-based association tests were performed to analyze four quantitative traits: the plasma concentrations of methadone R- and S-enantiomers and their respective metabolites. A significant single nucleotide polymorphism (SNP), rs17180299 (raw p = 2.24 × 10-8), was identified, accounting for 9.541% of the variation in the plasma concentration of the methadone R-enantiomer. In addition, 17 haplotypes were identified on SPON1, GSG1L, and CYP450 genes associated with the plasma concentration of methadone S-enantiomer. These haplotypes accounted for approximately one-fourth of the variation of the overall S-methadone plasma concentration. The association between the S-methadone plasma concentration and CYP2B6, SPON1, and GSG1L were replicated in another independent study. A gene expression experiment revealed that CYP2B6, SPON1, and GSG1L can be activated concomitantly through a constitutive androstane receptor (CAR) activation pathway. In conclusion, this study revealed new genes associated with the plasma concentration of methadone, providing insight into the genetic foundation of methadone metabolism. The results can be applied to predict treatment responses and methadone-related deaths for individualized MMTs.

Project description:IntroductionMethadone has long been regarded as an effective treatment for opioid dependence. However, many patients discontinue maintenance therapy because of its side effects, with one of the most common being sexual dysfunction. Buprenorphine is a proven alternative to methadone. This study aimed to investigate sexual dysfunction in opioid-dependent men on buprenorphine maintenance treatment (BMT) and methadone maintenance treatment (MMT). The secondary aim was to investigate the correlation between sexual dysfunction and the quality of life in these patients.MethodsTwo hundred thirty-eight men participated in this cross-sectional study. Four questionnaires were used, the Mini International Neuropsychiatric Interview, Opiate Treatment Index, Malay version of the International Index of Erectile Function 15 (Mal-IIEF-15), and World Health Organization Quality of Life-BREF Scale. Multivariate analysis of covariance was used to examine the relationship between MMT and BMT and the Mal-IIEF 15 scores while controlling for all the possible confounders.ResultsThe study population consisted of 171 patients (71.8%) on MMT and 67 (28.2%) on BMT. Patients in the MMT group who had a sexual partner scored significantly lower in the sexual desire domain (p < 0.012) and overall satisfaction (p = 0.043) domain compared with their counterparts in the BMT group. Similarly, patients in the MMT group without a sexual partner scored significantly lower in the orgasmic function domain (p = 0.008) compared with those in the BMT group without a partner. Intercourse satisfaction (p = 0.026) and overall satisfaction (p = 0.039) were significantly associated with the social relationships domain after adjusting for significantly correlated sociodemographic variables.ConclusionsSexual functioning is critical for improving the quality of life in patients in an opioid rehabilitation program. Our study showed that buprenorphine causes less sexual dysfunction than methadone. Thus, clinicians may consider the former when treating heroin dependents who have concerns about sexual function.

Dataset Information

GRK5 Is Associated with the Regulation of Methadone Dosage in Heroin Dependence.

Publications

GRK5 Is Associated with the Regulation of Methadone Dosage in Heroin Dependence.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets