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

Molecular Nutrition (I.N., Y.L., I.L., F.D.), Christian-Albrechts-University of Kiel, 24118 Kiel, Germany; Department of Epidemiology (E.F., H.B.) and Institute of Clinical Nutrition (J.Sp.), German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany; Institute of Epidemiology (H.Gr., C.G., , H.Go., A.D., H.-E.W., T.I.), GSF, National Research Center for Environment and Health, Neuherberg, D-85764 Munich, Germany; Federal Research Centre for Nutrition and Food (D.R., J.Sc.), Institute of Physiology and Biochemistry of Nutrition, D-24103 Kiel, Germany; Institute for Clinical Molecular Biology (S.S.), Christian-Albrechts-University of Kiel, D-24098 Kiel, Germany; German Center for Diabetes (W.R.), D-40225 Düsseldorf, Germany; and Department of Epidemiology (C.G., H.-E.W.), University of Munich, D-81377 Munich, Germany

Address all correspondence and requests for reprints to: Professor Frank Döring, Institute of Human Nutrition and Food Science, Department of Molecular Nutrition, Heinrich-Hecht-Platz 10, 24118 Kiel, Germany. E-mail: doering{at}molnut.uni-kiel.de.

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.