title: Association of prostaglandin E synthase 2 (PTGES2) Arg298His polymorphism with type 2 diabetes in two German study populations.
abstract: BACKGROUND
  On the basis of its chromosomal localization and its role in the synthesis of the antilipolytic compound prostaglandin E(2), 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.
  
  
  CONCLUSIONS
  We obtained evidence from two Caucasian study populations that the His298-allele of PTGES2 Arg298His confers to reduced risk of type 2 diabetes.
authors.affiliation: Molecular Nutrition, Christian-Albrechts-University of Kiel, Kiel, Germany.
authors.forename: Inke
authors.initials: I
authors.lastname: Nitz
authors.forename: Eva
authors.initials: E
authors.lastname: Fisher
authors.forename: Harald
authors.initials: H
authors.lastname: Grallert
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.forename: Diana
authors.initials: D
authors.lastname: Rubin
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Joachim
authors.initials: J
authors.lastname: Spranger
authors.forename: Inka
authors.initials: I
authors.lastname: Lindner
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rathmann
authors.forename: Henning
authors.initials: H
authors.lastname: Gohlke
authors.forename: Angela
authors.initials: A
authors.lastname: Döring
authors.forename: H-Erich
authors.initials: HE
authors.lastname: Wichmann
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schrezenmeir
authors.forename: Frank
authors.initials: F
authors.lastname: Döring
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001794:Blood Pressure / Q000502:physiology; D015153:Blotting, Western; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D000071876:Prostaglandin-E Synthases
chemical_list: D019746:Intramolecular Oxidoreductases; C000605863:PTGES2 protein, human; D000071876:Prostaglandin-E Synthases