Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts.
Previous studies of the association of the C17T polymorphism of the mu opiate receptor gene with substance dependence compared cases with substance dependence to controls and usually found no significant association.
Additional research is needed to determine whether these findings reflect no role for OPRM1 in determining risk for SD or whether another polymorphism in the gene influences receptor function and risk for SD.
Logistic regression analyses confirmed the association between OPRM1 variants and substance dependence, when sex and age of subjects and alleles, genotypes, haplotypes or diplotypes of five tag SNPs were considered.
A recent report (Hoehe et al., 2000) found a significant association between a specific combination of OPRM1 single nucleotide polymorphisms (SNPs) and substance dependence.
Our findings and analyses suggest that the OPRM1 +118 polymorphism is a general risk gene for substance dependence, but is not specific to a particular substance.
In both patient samples and by both methods we were unable to corroborate the hypothesis of OPRM1A118G polymorphism as a particular risk factor for any kind of substance dependence including opioid addiction.
The three opioid receptor genes, and in particular the mu and delta loci (OPRM1 and OPRD1, respectively), are compelling candidates to influence risk for substance dependence.
Detection of genetic variation affecting OPRM1 expression or mu opioid receptor function would be an important step towards understanding the origins of inter-individual variation in response to mu opioid receptor ligands and in diseases of substance dependence.
Further studies of the association between alleles of the OPRM1 gene and substance dependence appear warranted, particularly if they use a family-based approach to control for population stratification.
Connect function from IPA My Pathway toolbox showed that DRD2 is the gene common to both the list of genetic variations associated with all three addiction phenotypes and the components of the brain neuronal signaling network involved in substance addiction.
The effects differed for substance dependence groups as the direction of the correlations with DRD2 were opposite to what was seen in subjects without these dependencies.
The finding of an association between substance dependence and the DRD2 gene TaqIA SNP only in males suggests the existence of gender-specific differences in the genetic underpinnings of substance dependence.
Previous studies, although not all, have demonstrated associations between the DRD2 TaqI and the DRD4 exon III variable number tandem repeat (VNTR) polymorphisms and substance dependence.
Together, these studies suggest that the conflicting findings from case-control studies of the association between alleles of DRD2 and substance dependence may be attributable to population stratification in some samples.
Reports of allelic associations were originally made with alcoholism, but were then extended to other psychiatric disorders; there has been a series of positive reports suggesting an association between DRD2 alleles and substance dependence in European-American (EA) subjects.
The cannabinoid receptor 1 protein regulates both the endocannabinoid and dopaminergic neurobiological systems, and polymorphisms in the cannabinoid receptor gene, CNR1, have been associated previously with substance dependence.
Recently, an (AAT)n triplet repeat polymorphism within the cannabinoid receptor gene CNR1 has been found to be associated with both schizophrenia and substance dependence, and to modulate the P300 potential.