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Sequence variations in the mu-opioid receptor gene (OPRM1) associated with human addiction to heroin
Abstract
Human mu-opioid receptor (OPRM1) is the major site for the analgesic action of most opioid drugs such as morphine, methadone and heroin. It was previously reported that a single nucleotide polymorphism (SNP) in exon1 (c.118A-->G) of OPRM1 might modestly alter the affinity in beta-endorphin-Mu interaction. Using denaturing high performance liquid chromatography (DHPLC) the complete coding region of the OPRM1 gene was screened for SNPs in Han-Chinese heroin addicts and normal control. Three novel SNPs were detected, one in exon3, one in intron3 and one in the 3' untranslated region. The SNP c.118A-->G reportedly altered the interaction of Mu receptor with opioid had no statistically significant correlation with heroin addition in Han Chinese. However, addicted subjects with the SNP in intron2 (IVS2 +31G-->A) tended to show much higher heroin intake dosages than those without this SNP. We also observed that individuals carrying both SNP c.118A-->G and IVS2 +31G-->A consumed relatively more drugs compared to other addicts. Thus our study further highlights the importance of studing the various regions of the mu opioid receptor gene, coding as well as non-coding, for genetic markers that may be linked to, or directly contribute to opioid drug-seeking behavior.
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“This might be the ability of nicotine to reduce the turnover and release of dopamine through occupying mu or kappa receptors of endorphins or through cholinergic receptors for nicotine[1920] presented on dopaminergic cells. Local reduction of dopamine could lead to over-production of prolactin by lactotroph cells.[21]”
From Nicotine alters male reproductive hormones in male albino rats: The role of cessation (2013) · cites this paper as [21]
In the citing paper
“Other mutations in this gene are associated to heroin addiction178, and pain perception179, but also sociality traits180.”
From A catalog of single nucleotide changes distinguishing modern humans from archaic hominins (2019) · cites this paper as [178]
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Metadata
- Authors
- Shi, J., Hui, L., Xu, Y., Wang, F., Huang, W., & Hu, G.
- Affiliations
- Chinese Academy of Sciences (CN)
- Chinese National Human Genome Center at Shanghai (CN)
- Venue
- Human Mutation
- Publisher
- Hindawi Limited
- Published
- 2002-03-18
- Volume
- 19
- Issue
- 4
- Pages
- 459-460
- ISSN
- 1059-7794 (ISSN-L)
- 1098-1004
- OpenAlex
- W2017514322
- Cited by
- 140
- References
- 19
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 8 · 2018: 4 · 2017: 6 · 2016: 5 · 2015: 6 · 2014: 6 · 2013: 10 · 2012: 8
- FWCI
- 2.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Mutation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
- Keywords
- mu-opioid receptor, OPRM1, heroin addiction, opioid use disorder, single nucleotide polymorphisms, genetic susceptibility, Han Chinese, 3' untranslated region, drug-seeking behavior
- MeSH terms
- China, Chromatography, High Pressure Liquid, Exons, Gene Frequency, Genetic Testing, Genotype, Heroin Dependence, Humans, Introns, Phenotype, Genetic Variation, Receptors, Opioid, mu, Genetic Predisposition to Disease, 3' Untranslated Regions, Asian People
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