Details

Autor(en) / Beteiligte

• Pang, Grace SY
• Wang, Jingbo
• Wang, Zihua
• Goh, Cynthia
• Lee, Caroline GL

Titel

The G allele of SNP E1/A118G at the µµ-opioid receptor gene locus shows genomic evidence of recent positive selection

Ist Teil von

• Pharmacogenomics, 2009-07, Vol.10 (7), p.1101-1109

Ort / Verlag

Future Medicine Ltd

Erscheinungsjahr

2009

Beschreibungen/Notizen

• Opioid drug response and pain perception differs greatly amongst different individuals. The µµ-opioid receptor (MOR) is the main receptor target for important opioid analgesics. As SNPs may contribute to interindividual differences in drug response, signatures of recent positive selection (RPS) were utilized to seek out potentially functional SNPs in the gene in order to facilitate the prioritization of SNPs for evaluation in genetic association studies. Out of over 1000 SNPs at the locus, 184 high-frequency SNPs were interrogated for signatures of RPS. A total of five SNPs (four noncoding and one nonsynonymous coding) demonstrated evidence of RPS. Significantly, the nonsynonymous E1/A118G SNP, which was previously reported to be functionally important, showed evidence of RPS. This reaffirms the feasibility of utilizing 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.