The G Allele of SNP E1/A118G at the µ-Opioid Receptor Gene Locus Shows Genomic Evidence of Recent Positive Selection

Abstract

Opioid drug response and pain perception differs greatly amongst different individuals. The micro-opioid receptor (MOR) is the main receptor target for important opioid analgesics. As SNPs may contribute to interindividual differences in drug response, in silico signatures of recent positive selection (RPS) were utilized to seek out potentially functional SNPs in the MOR gene in order to facilitate the prioritization of SNPs for evaluation in genetic association studies. Out of over 1000 SNPs at the MOR locus, 184 high-frequency SNPs were interrogated for signatures of RPS. A total of five SNPs (four noncoding and one nonsynonymous coding) demonstrated in silico evidence of RPS. Significantly, the nonsynonymous E1/A118G SNP, which was previously reported to be functionally important, showed in silico evidence of RPS. This reaffirms the feasibility of utilizing in silico signatures of RPS to identify potentially functionally significant SNPs for association studies. Interestingly, the positively selected G allele of this RPS SNP was also predicted to create a novel exon splice enhancer as well as p53 binding sites.