Association of Prostaglandin E Synthase 2 (PTGES2) Arg298His Polymorphism with Type 2 Diabetes in Two German Study Populations

Context: On the basis of its chromosomal localization and its role in the synthesis of the antilipolytic compound prostaglandin E2, the prostaglandin E synthase 2 (PTGES2) is a candidate gene for type 2 diabetes. Objective: The aim of the present study was to investigate whether genetic variants in the PTGES2 gene are associated with type 2 diabetes. Results: Sequencing of the PTGES2 gene revealed one nonsynonymous coding single-nucleotide polymorphism (SNP) (Arg298His, rs13283456) and a previously unknown promoter SNP g.-417G>T. Both SNPs and additional haplotype tagging SNPs (rs884115, rs10987883, rs4837240) were genotyped in a nested case-control study of 192 incident type 2 diabetes subjects and 384 controls (European Prospective Investigation into Cancer and Nutrition-Potsdam). Carriers of the minor allele of Arg298His had a lower risk to develop the disease [odds ratio (OR) 0.63, 95% confidence interval (CI) 0.41–0.97, P = 0.04], compared with homozygous individuals with the common allele. The PTGES2 Arg298His polymorphism was reinvestigated in a population-based cross-sectional study (Cooperative Health Research in the Augsburg Region) consisting of 239 individuals with impaired glucose tolerance, 226 with type 2 diabetes, and 863 normoglycemic controls. In this study population, the Arg298His polymorphism was significantly associated with impaired glucose tolerance (OR 0.68, 95% CI 0.50–0.93, P = 0.007) and type 2 diabetes (OR 0.61, 95% CI 0.43–0.86, P = 0.004). A pooled analysis of data from both study populations revealed reduced risk of type 2 diabetes (OR 0.62, 95% CI 0.47–0.81, P = 0.0005) in PTGES2 298His allele carriers. Conclusion: We obtained evidence from two Caucasian study populations that the His298-allele of PTGES2 Arg298His confers to reduced risk of type 2 diabetes.