RGD Reference Report - Haplotypes at the OPRM1 locus are associated with susceptibility to substance dependence in European-Americans. - Rat Genome Database

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Haplotypes at the OPRM1 locus are associated with susceptibility to substance dependence in European-Americans.

Authors: Luo, Xingguang  Kranzler, Henry R  Zhao, Hongyu  Gelernter, Joel 
Citation: Luo X, etal., Am J Med Genet B Neuropsychiatr Genet. 2003 Jul 1;120B(1):97-108. doi: 10.1002/ajmg.b.20034.
RGD ID: 401827942
Pubmed: PMID:12815747   (View Abstract at PubMed)
DOI: DOI:10.1002/ajmg.b.20034   (Journal Full-text)

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. We used a newly implemented permutation method to evaluate statistical significance. In EAs, a significant difference in haplotype frequency distributions was found between controls and "alcohol + opioid" dependent patients (P = 0.0036). This finding is also supported by logistic regression analysis and a simulation method. The frequencies of allele -2044A and haplotypes including -2044A are higher in these patients than in controls. In AAs, no allele, haplotype, or genotype frequencies were significantly different between cases and controls. There were highly significant differences in the allele, haplotype, and genotype frequencies between EA and AA controls. 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.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
OPRM1Humanopiate dependence  IAGP associated with alcohol dependence:DNA:SNP and haplotypes: :-2044C>A (human)RGD 
Oprm1Ratopiate dependence  ISOOPRM1 (Homo sapiens)associated with alcohol dependence:DNA:SNP and haplotypes: :-2044C>A (human)RGD 
Oprm1Mouseopiate dependence  ISOOPRM1 (Homo sapiens)associated with alcohol dependence:DNA:SNP and haplotypes: :-2044C>A (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Oprm1  (opioid receptor, mu 1)

Genes (Mus musculus)
Oprm1  (opioid receptor, mu 1)

Genes (Homo sapiens)
OPRM1  (opioid receptor mu 1)


Additional Information