Population-specific genetic background for the OPRM1 variant rs1799971 (118A>G): implications for genomic medicine and functional analysis.
- Authors
- Levran, Orna; Kreek, Mary Jeanne
- Year
- 2021
- Journal
- Molecular psychiatry
- PMID
- 33037305
- DOI
- 10.1038/s41380-020-00902-4
The mu-opioid receptor (MOR, OPRM1) has important roles in diverse functions including reward, addiction, and response to pain treatment. SNP rs1799971 (118A > G, N40D) which occur at a high frequency (40-60%) in Asia and moderate frequency (15%) in samples of European ancestry, is the only common coding variant in the canonical transcript, in non-African populations. Despite extensive studies, the molecular consequences of this variation remained unresolved. The aim of this study was to determine the genetic background of the OPRM1 region of 118G in four representative populations and to assess its potential modulatory effect. Seven common haplotypes with distinct population distribution were identified based on seven SNPs. Three haplotypes carry the 118G and additional highly linked regulatory SNPs (e.g., rs9383689) that could modulate the effect of 118G. Extended analysis in the 1000 Genomes database (n = 2504) revealed a common East Asian-specific haplotype with a different genetic background in which there are no variant alleles for an upstream LD block tagged by the eQTL rs9397171. The major European haplotype specifically includes the eQTL intronic SNP rs62436463 that must have arisen after the split between European and Asian populations. Differentiating between the effect of 118G and these SNPs requires specific experimental approaches. The analysis also revealed a significant increase in two 118A haplotypes with eQTL SNPs associated with drug addiction (rs510769) and obesity (rs9478496) in populations with native Mexican ancestry. Future studies are required to assess the clinical implication of these findings.
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|---|---|---|
| Multi-trait genome-wide association study of opioid addiction: OPRM1 and beyond. | 2022 | 36207451 |
External
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|---|---|---|---|---|
| A review of the existing pharmacogenomic literature of naltrexone for use in alcohol use disorder. | Counts C et al. | — | 2025 | → |
| Molecular and Environmental Determinants of Addictive Substances. | Lorek M et al. | — | 2024 | → |
| The effects of OPRM1 118A>G on methadone response in pain management in advanced cancer at end of life. | Haupt LM et al. | — | 2024 | → |
| Association between rs1799971 in the mu opioid receptor gene and methadone maintenance treatment response. | Xie X et al. | — | 2022 | → |
| Associations of the A118G OPRM1 polymorphism with sociotropy and interpersonal sensitivity. | Suzuki A et al. | — | 2022 | → |
| Multi-trait genome-wide association study of opioid addiction: OPRM1 and beyond. | Gaddis N et al. | — | 2022 | → |
| Mu opioid receptor gene variant modulates subjective response to smoked cannabis. | Bourgault Z et al. | — | 2022 | → |
| Pharmacogenomics of Cancer Pain Treatment Outcomes in Asian Populations: A Review. | Satkunananthan SE et al. | — | 2022 | → |