Lack of association between the A118G polymorphism of the mu opioid receptor gene (OPRM1) and opioid dependence: A meta-analysis.
- Authors
- Coller, Janet K; Beardsley, Julia; Bignold, James; Li, Yibai; Merg, Florence; Sullivan, Thomas; Cox, Timothy C; Somogyi, Andrew A
- Year
- 2009
- Journal
- Pharmacogenomics and personalized medicine
- PMID
- 23226031
- PMCID
- PMC3513197
Mu opioid receptor (OPRM1) gene variants, particularly the common A118G single nucleotide polymorphism (SNP), are among the most frequently studied candidate genes associated with opioid dependence. However, despite numerous case-control studies and meta-analyses, no definitive conclusion has been reached regarding the association of the A118G SNP and risk of developing opioid dependence. This study aimed to resolve this discrepancy by reinvestigating the association between A118G SNP allelic, and for the first time, genotype frequencies and opioid dependence. A meta-analysis of sixteen case-control studies of opioid dependence was performed with a total of 5169 subjects. No association between the A118G allele (P = 0.23) and genotype (P = 0.34) frequencies and opioid dependence was found. However, significant heterogeneity between studies precluded highly definitive conclusions. In addition, the possibility that other OPRM1 SNPs albeit rarer may influence the risk of opioid dependence remains to be investigated at this level. Nonetheless, despite no evidence of a direct association with risk of dependence, A118G may still influence the pharmacological response to opioids impacting on an individual's dosage requirements.
Forest plot depicting the odds ratios (OR) and 95% confidence interval (CI) of each of the 13 studies investigating the association between A118G OPRM1 genotype frequencies and opioid dependence. The solid line represents an OR of 1 and the stippled line represents the pooled OR.
Begg’s funnel plot of the 13 studies investigating the association between A118G OPRM1 genotype frequencies and opioid dependence.
Forest plot depicting the odds ratios (OR) and 95% confidence interval (CI) of each of the 13 studies investigating the association between A118G OPRM1 genotype frequencies and opioid dependence stratified as majority Caucasian and Asian ethnic groups. The solid line represents an OR of 1 and the stippled line represents the pooled OR.
Forest plot depicting the odds ratios (OR) and 95% confidence interval (CI) of each of the 16 studies investigating the association between A118G OPRM1 allele frequencies and opioid dependence. The solid line represents an OR of 1 and the stippled line represents the pooled OR, P = 0.000 equivalent to P < 0.0001.
Begg’s funnel plot of the 16 studies investigating the association between A118G OPRM1 allele frequencies and opioid dependence.
Forest plot depicting the odds ratios (OR) and 95% confidence interval (CI) of each of the 16 studies investigating the association between A118G OPRM1 allele frequencies and opioid dependence stratified as majority Caucasian and Asian ethnic groups. The solid line represents an OR of 1 and the stippled line represents the pooled OR, P = 0.000 equivalent to P < 0.0001.
| Name | Type |
|---|---|
| 16 studies local | cohort |
| A118G allele local | variant |
| A118G polymorphism local | variant |
| A118G SNP | variant |
| addiction | phenotype |
| African-Americans | cohort |
| age | phenotype |
| alcohol | phenotype |
| allele-specific PCR local | drug |
| Analgesic response to opioids local | phenotype |
| Asian | cohort |
| beta-endorphin | drug |
| Bond study local | cohort |
| brain reward pathway local | anatomy |
| Brain-reward pathway local | anatomy |
| buprenorphine | drug |
| case subjects | cohort |
| Caucasian | cohort |
| cocaine | phenotype |
| Coller et al unpublished local | cohort |
| control group | cohort |
| control groups | cohort |
| control subjects | cohort |
| Crowley study local | cohort |
| denaturing high performance liquid chromatography local | drug |
| depression | phenotype |
| Drakenberg cohort local | cohort |
| Drakenberg study local | cohort |
| drug dependence | phenotype |
| DSM-III-R local | phenotype |
| DSM-IV | phenotype |
| endogenous opioids | drug |
| environmental factors | drug |
| G allele | variant |
| genetic factors | cohort |
| G/G genotype local | variant |
| G variant allele local | variant |
| healthy controls | cohort |
| heavy drinking | phenotype |
| Hispanic | phenotype |
| Indian | cohort |
| Li study local | cohort |
| mainland Asia local | cohort |
| major psychiatric disorders | phenotype |
| Methadone | drug |
| Methadone maintenance opioid-dependent subjects local | cohort |
| morphine | drug |
| morphine dependence local | phenotype |
| multiplex sequence comparison technique local | drug |
| mu opioid receptor | drug |
| Neurological adaptations local | phenotype |
| nicotine | drug |
| opiates | drug |
| opioid | drug |
| opioid dependence | phenotype |
| opioid tolerance | phenotype |
| OPRM1 | cohort |
| OPRM1 A118G | cohort |
| OPRM1 Asn40Asp (A118G) local | variant |
| PCR | drug |
| pentazocine local | drug |
| Pharmacological adaptations local | phenotype |
| Prescription opiates local | drug |
| psychiatric disorders | phenotype |
| Psychosocial factors | phenotype |
| Reinforcing effect of nicotine local | phenotype |
| restriction fragment length polymorphism local | drug |
| schizophrenia | phenotype |
| sex | phenotype |
| Shi study local | cohort |
| substance use | phenotype |
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| Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts. | Schwantes-An TH et al. | — | 2016 | → |
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| Functional mu opioid receptor polymorphism (OPRM1 A(118) G) associated with heroin use outcomes in Caucasian males: A pilot study. | Woodcock EA et al. | — | 2015 | → |
| Genetic ancestry as an effect modifier of naltrexone in smoking cessation among African Americans: an analysis of a randomized controlled trial. | Bress A et al. | — | 2015 | → |
| Association of OPRD1 polymorphisms with heroin dependence in a large case-control series. | Nelson EC et al. | — | 2014 | → |
| Impact of ABCB1 and CYP2B6 genetic polymorphisms on methadone metabolism, dose and treatment response in patients with opioid addiction: a systematic review and meta-analysis. | Dennis BB et al. | — | 2014 | → |
| OPRM1 rs1799971 polymorphism and opioid dependence: evidence from a meta-analysis. | Haerian BS et al. | — | 2013 | → |
| ABCB1 haplotype and OPRM1 118A > G genotype interaction in methadone maintenance treatment pharmacogenetics. | Barratt DT et al. | — | 2012 | → |