Pharmacogenetics of the prostaglandin-endoperoxide synthase 2 (PTGS-2) 5' and 3' untranslated regions in three distinct Asian populations.

Abstract

Cyclooxygenase-2 (COX-2) is an enzyme induced in response to mitogens, tumour promoters, and cytokines. Gene expression of COX-2 is found to be upregulated in solid tumours. Polymorphisms in regulatory regions of PTGS-2 encoding COX-2 were demonstrated to influence COX-2 expression levels and alter risk association to various cancers, notably colorectal cancer.

This study aimed to identify PTGS-2 polymorphisms present in three distinct Asian ethnicities in Singapore: Chinese, Malay and Indian. In total, 66 SNPs were identified via direct sequencing, of which 25 were novel SNPs and 40 SNPs were found in regulatory regions. There were significant inter-ethnic variations in genotypic frequencies of -1329A>G (rs689466) and IVS1+145A>G (rs11567820) (P=0.047 and 0.009, respectively). Linkage disequilibrium (LD) analysis showed differences in LD patterns across the three ethnicities. Haplotype analysis identified variations in haplotype blocks and haplotypes in each ethnicity

and a total of nine haplotype-tagging SNPs (htSNPs) were identified.

This study comprehensively evaluated the genetic variation of PTGS-2, revealing significant differences in the genetic pattern of PTGS-2 polymorphisms among the three ethnicities. These differences may account for the difference in risk association of cancer or pharmacogenetic association. Further confirmational investigations in larger cohort and functional evaluations may warrant potential insights to the role of PTGS-2 polymorphisms in Asian population.