American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
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Am. J. Med. Genet. B Neuropsychiatr. Genet. · Aug 2003
Association between human mu-opioid receptor gene polymorphism, pain tolerance, and opioid addiction.
Central to both pain responses and opioid addiction is activity at the micro -opioid receptor. To explore the role of the micro -opioid receptor gene (OPRM) in human pain tolerance and opioid addiction, we examined the relationships among OPRM genotype and experimental pain tolerance in opioid addicts in methadone treatment (n = 50) and healthy normal controls (n = 59). Pain phenotype (pain tolerant vs. pain intolerant) was operationalized as tolerance to a standardized noxious stimulus (either thermal or mechanical), and dichotomized based on distribution. ⋯ Although the established relationship between the phenotypes of opioid addiction and pain intolerance was validated (P = 0.02), genotype differed neither between addict-affected vs. control, nor pain tolerant vs. intolerant subjects. The variant A118G was absent in all individuals and the C17T polymorphism appeared in only three African-American individuals (two addicts and one control). The absence of this polymorphism, the small sample size and the heterogeneous ethnic backgrounds of participants in the pilot study allow only tentative conclusions based on the results, thus the role of the opioid receptor in pain and opioid reward response remains uncertain.
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Am. J. Med. Genet. B Neuropsychiatr. Genet. · Jul 2003
Comparative StudyHaplotypes at the OPRM1 locus are associated with susceptibility to substance dependence in European-Americans.
Our objective was to investigate the relationship between the gene encoding the mu-opioid receptor (OPRM1) and susceptibility to substance dependence in European-American (EA) and African-American (AA) subjects. Eight single nucleotide polymorphisms (SNPs) at the OPRM1 locus, i.e., -2044C/A, -1793T/A, -1699insT, -1469T/C, -1320A/G, -111C/T, +17C/T (Ala6Val), and +118A/G (Asn40Asp) were genotyped in 676 subjects: 318 EA subjects and 124 AA subjects with substance dependence, and 179 EA normal controls, and 55 AA normal controls. Affection status was defined by each unique combination of alcohol, cocaine, and opioid dependence and analysis of association examined in relation to the possible combinations. ⋯ Four of the variants [-1793T/A, -1699insT, -1320A/G, and -111C/T] are in virtually complete linkage disequilibrium (LD) to compose a sequence pattern, which does not associate with any of the seven categories of substance dependence. In EAs, allele -2044A and haplotypes that include -2044A are the susceptibility allele and haplotypes for substance dependence. These findings suggest that OPRM1 may play a role in the pathophysiology of substance dependence and this role is population- and diagnosis-specific.