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This version published online on June 12, 2007
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2006-2550
A more recent version of this article appeared on August 1, 2007
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Right arrow Diabetes and Insulin

Submitted on November 20, 2006
Accepted on May 31, 2007

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

Inke Nitz, Eva Fisher, Harald Grallert, Yun Li, Christian Gieger, Diana Rubin, Heiner Boeing, Joachim Spranger, Inka Lindner, Stefan Schreiber, Wolfgang Rathmann, Henning Gohlke, Angela Döring, H. -Erich Wichmann, Jürgen Schrezenmeir, Frank Döring*, and Thomas Illig

Molecular Nutrition, Christian-Albrechts-University of Kiel, Kiel, Germany; Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Epidemiology, GSF - National Research Center for Environment and Health, Neuherberg, Munich, Germany; Federal Research Centre for Nutrition and Food, Institute of Physiology and Biochemistry of Nutrition, Kiel, Germany; Institute of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute for Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Germany; German Center for Diabetes (DDZ), Düsseldorf, Germany; Chair of Epidemiology, University of Munich, Munich, Germany

* To whom correspondence should be addressed. E-mail: doering{at}molnut.uni-kiel.de.

Context: On the basis of its chromosomal localisation 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 if genetic variants in the PTGES2 gene are associated with type 2 diabetes.

Results: Sequencing of the PTGES2 gene revealed one non-synonymous cSNP (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 (EPIC-Potsdam). Carriers of the minor allele of Arg298His had a lower risk to develop the disease (OR: 0.63, 95% CI: 0.41-0.97, p: 0.04) compared to homozygous individuals with the common allele. The PTGES2 Arg298His polymorphism was reinvestigated in a population based cross-sectional study (KORA) consisting of 239 individuals with impaired glucose tolerance (IGT), 226 with type 2 diabetes, and 863 normoglycemic controls. In this study population, the Arg298His polymorphism was significantly associated with IGT (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.
Key words: prostaglandin E synthase 2 • polymorphism • type 2 diabetes mellitus






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