Haplotype block structure of the genomic region of the mu opioid receptor gene.
- Authors
- Levran, Orna; Awolesi, Olaoluwakitan; Linzy, Shirley; Adelson, Miriam; Kreek, Mary Jeanne
- Year
- 2011
- Journal
- Journal of human genetics
- PMID
- 21160491
- DOI
- 10.1038/jhg.2010.150
- PMCID
- PMC3075619
The opioid system is involved in the action of opiate drugs, opioid addiction, pain experience and analgesia. Individual differences in opioid effect may be attributed in part to genetic variations. Long-range cis regulatory elements and intronic variants are potential sources of functional diversity. Recently, we have detected association of two intronic OPRM1 variants with heroin addiction in European Americans. In this study, we analyzed the genetic variations in the OPRM1 100โkb 5'-flanking region and intron 1 in the HapMap Caucasian population. Four major linkage disequilibrium blocks were identified, consisting of 28, 22, 15 and 42 single-nucleotide polymorphisms (SNPs), respectively. The locations of these blocks are (-100 to -90), (-90 to -67), (-20 to -1) and (+1 to +44)โkb, respectively. The two intronic variants, indicated in our recent study, are part of a distinct haplogroup that includes SNPs from intron 1, and the proximal 5' region. The 118G (rs1799971) allele is part of a different haplogroup that includes several variants in the distal 5' region that may have a regulatory potential. These findings were corroborated by genotyping eight SNPs in a sample of European Americans and suggest an extended OPRM1 locus with potential new regulatory regions.
a. Schematic representation of the OPRM1 gene region and the location of the 8 SNPs genotyped: rs1551808 (1), rs7758009 (2), rs7760028 (3), rs1074287 (4), rs1799971 (118A>G, 5), rs510769 (6), rs3778146 (7), and rs3778151 (8). Black boxes indicate exons, open boxes indicate untranslated regions (UTR) and dotted boxes indicate alternatively spliced exons.b. A customized view from the UCSC genome browser that covers 100 kb of the 5โฒ region, exon 1 and 50 Kb of intron 1, showing pair-wise alignment of each of four species with the human genome. The tracks from top to bottom show the positions of segments aligned with the indicated comparison species. Green bars indicate conserved regions.
a. Plot of pair-wise linkage disequilibrium (LD) of the 150 kb OPRM1 genomic region, in the HapMap CEU sample. The plot is not drawn to scale and the arrows show the correct position of the SNPs. The color scheme indicates the magnitude of r2. Black blocks indicate r2= 1, and white blocks indicate r2= 0. b. The pattern and frequency of the major haplogroups in this population. The height of the boxes is proportional to the frequency in the population. Blue boxes indicate variant alleles, yellow boxes indicate reference alleles and gray boxes indicate all the other haplogroups.
| Name | Type |
|---|---|
| 118G local | variant |
| 118G/118G genotype group local | cohort |
| 118G haplogroup local | variant |
| A118G SNP | variant |
| A allele | cohort |
| ABI Prism 3700 local | drug |
| ABI Prismยฎ 7900 sequence detection system local | drug |
| addiction | phenotype |
| African | cohort |
| African American | cohort |
| African HapMap local | cohort |
| African samples | cohort |
| AmpErase uracil-N-glycosylate local | drug |
| Applied Biosystems (ABI) local | drug |
| Asian | cohort |
| beta-endorphin | drug |
| block 1 SNPs local | variant |
| block 1 variants local | variant |
| block 2 local | cohort |
| block 3 local | cohort |
| block 3 haplogroup local | variant |
| block 4 intron 1 variants local | variant |
| cases | cohort |
| Caucasians | cohort |
| Caucasian sample | cohort |
| CEPH diversity panel local | cohort |
| CEU | cohort |
| controls | cohort |
| cortisol | drug |
| drug dependence | phenotype |
| European ancestry | cohort |
| European population | cohort |
| exploratory representative sample local | cohort |
| GeneAmpยฎ PCR 9700 local | drug |
| haplogroup local | variant |
| haplogroup 3 local | cohort |
| haplogroup block 1 local | variant |
| Haploview version 4.2.36 local | drug |
| HapMap3 | cohort |
| HapMap African population local | cohort |
| HapMap Asian populations local | cohort |
| HapMap CEU | cohort |
| healthy controls | cohort |
| heavy drinking | phenotype |
| heroin addiction subjects local | cohort |
| HPA activation local | phenotype |
| humans | cohort |
| INT1 local | cohort |
| INT1 local | variant |
| INT1 haplogroup local | cohort |
| INT1 haplogroup local | variant |
| International Hapmap Project | cohort |
| International HapMap Project Phase 2 local | cohort |
| intron 1 sequence local | variant |
| intron 1 variant local | variant |
| IPCEF1 local | gene |
| IVS1 local | variant |
| IVS1/118G genotype group local | cohort |
| IVS1/118G subgroup local | cohort |
| IVS1 SNP #6 local | variant |
| IVS1 SNP #7 local | variant |
| IVS1 SNP #8 local | variant |
| IVS1 SNPs local | variant |
| JPN/CHB local | cohort |
| JPT/CHB local | cohort |
| linked variants local | variant |
| Methadone | drug |
| naloxone | drug |
| naltrexone | drug |
| non-coding variants (distant from OPRM1) local | variant |
| opioid | drug |
| opioid adverse effects local | phenotype |
| Opioid adverse effects local | phenotype |
| opioid dependence | phenotype |
| opioid response | phenotype |
| opioid reward | phenotype |
| opioid tolerance | phenotype |
| OPRM1 | cohort |
| OPRM1 A118G | cohort |
| OPRM1 alternative exon local | variant |
| OPRM1 intron 1 SNP local | variant |
| OPRM1 intron 1 variant #6 local | variant |
| OPRM1 intron 1 variant #8 local | variant |
| OPRM1 splice variant | variant |
| original sample9 local | cohort |
| Others local | cohort |
| PADI3 local | gene |
| pain | phenotype |
| pain perception | phenotype |
| pain sensitivity | phenotype |
| Platinum PCR Supermix local | drug |
| positive response to heroin after first use local | phenotype |
| Primer3.37 local | drug |
| REF local | cohort |
| REF local | variant |
| REF/118G genotype group local | cohort |
| REF/REF genotype group local | cohort |
| REF/REF subgroup local | cohort |
| response to naltrexone treatment | phenotype |
| response to opiates local | phenotype |
| RGS17 local | gene |
| rodents | cohort |
| rs10457090 local | variant |
| rs1074287 | variant |
| rs11966947 local | variant |
| rs12174208 local | variant |
| rs12527423 local | variant |
| rs1551808 local | variant |
| rs17084868 local | variant |
| rs17084870 local | variant |
| rs1799971 | variant |
| rs3778146 local | variant |
| rs3778151 | variant |
| rs3778152 local | variant |
| rs510769 | variant |
| rs563649 | variant |
| rs6936615 local | variant |
| rs7748401 local | variant |
| rs7758009 local | variant |
| rs7760028 local | variant |
| rs9384167 local | variant |
| rs9478498 local | variant |
| rs9478499 local | variant |
| SDS 2.1 software local | drug |
| Sequencer 4.5 local | drug |
| SNP #1 local | variant |
| SNP -1320A>G local | variant |
| SNP -1699insT local | variant |
| SNP -1793T>A local | variant |
| SNP #2 local | variant |
| SNP -2044C>A local | variant |
| SNP #3 local | variant |
| SNP #5 local | variant |
| SNP -554G>A local | variant |
| SNP #6 local | variant |
| SNP #8 local | variant |
| SNPs in intron 1 local | variant |
| study cohort | cohort |
| Subgroup 1 local | cohort |
| Subgroup 2 local | cohort |
| Subgroup 4 local | cohort |
| substance use | phenotype |
| TaqMan assay | drug |
| TaqManยฎ Pre-Designed SNP Genotyping Assay local | drug |
| TaqManยฎ technology local | drug |
| TaqMan Universal PCR Master Mix | drug |
| treatment response | phenotype |
| vulnerability to develop opioid addiction local | phenotype |
| YRI | cohort |
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In this knowledge base
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Multi-trait genome-wide association study of opioid addiction: OPRM1 and beyond. | Gaddis N et al. | โ | 2022 | โ |
| Population-specific genetic background for the OPRM1 variant rs1799971 (118A>G): implications for genomic medicine and functional analysis. | Levran O et al. | โ | 2021 | โ |
| A hominid-specific shift in cerebellar expression, upstream retrotransposons, and a potential cis-regulatory mechanism: bioinformatics analyses of the mu-opioid receptor gene. | Levran O et al. | โ | 2020 | โ |
| Association of OPRM1 Functional Coding Variant With Opioid Use Disorder: A Genome-Wide Association Study. | Zhou H et al. | โ | 2020 | โ |
| Current status of opioid addiction treatment and related preclinical research. | Kreek MJ et al. | โ | 2019 | โ |
| The frequency of <i>DRD2</i> rs1076560 and <i>OPRM1</i> rs1799971 in substance use disorder patients from the United Arab Emirates. | Alblooshi H et al. | โ | 2018 | โ |
| A cis-eQTL in OPRM1 is Associated with Subjective Response to Alcohol and Alcohol Use. | Otto JM et al. | โ | 2017 | โ |
| Contribution of Genetic Polymorphisms and Haplotypes in DRD2, BDNF, and Opioid Receptors to Heroin Dependence and Endophenotypes Among the Han Chinese. | Gao X et al. | โ | 2017 | โ |
| Dimensionality and Genetic Correlates of Problem Behavior in Low-Income African American Adolescents. | Latendresse SJ et al. | โ | 2017 | โ |
| Opioids Resistance in Chronic Pain Management. | Morrone LA et al. | โ | 2017 | โ |
| The ฮผ-opioid receptor nonsynonymous variant 118A>G is associated with prolonged abstinence from heroin without agonist treatment. | Levran O et al. | โ | 2017 | โ |
| Cis-Expression Quantitative Trait Loci Mapping Reveals Replicable Associations with Heroin Addiction in OPRM1. | Hancock DB et al. | โ | 2015 | โ |
| Human population genetic structure detected by pain-related mu opioid receptor gene polymorphisms. | Lรณpez Soto EJ et al. | โ | 2015 | โ |
| TACR1 gene polymorphism and sex differences in postoperative nausea and vomiting. | Hayase T et al. | โ | 2015 | โ |
| Association of ฮผ-opioid receptor gene (OPRM1) haplotypes with postoperative nausea and vomiting. | Sugino S et al. | โ | 2014 | โ |
| Inosine triphosphate pyrophosphohydrolase (ITPA) polymorphic sequence variants in Chinese ALL children and possible association with mercaptopurine related toxicity. | Ma X et al. | โ | 2014 | โ |
| Introduction to deep sequencing and its application to drug addiction research with a focus on rare variants. | Wang S et al. | โ | 2014 | โ |
| OPRM1 A118G gene variant and postoperative opioid requirement: a systematic review and meta-analysis. | Hwang IC et al. | โ | 2014 | โ |
| OPRM1 genetic polymorphisms are associated with the plasma nicotine metabolite cotinine concentration in methadone maintenance patients: a cross sectional study. | Chen YT et al. | โ | 2013 | โ |
| A118G Mu Opioid Receptor polymorphism increases inhibitory effects on CaV2.2 channels. | Lopez Soto EJ et al. | โ | 2012 | โ |
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