Association of prostaglandin E synthase 2 (PTGES2) Arg298His polymorphism with type 2 diabetes in two German study populations.
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.
Nitz
Inke
I
Molecular Nutrition, Christian-Albrechts-University of Kiel, Kiel, Germany.
Fisher
Eva
E
Grallert
Harald
H
Li
Yun
Y
Gieger
Christian
C
Rubin
Diana
D
Boeing
Heiner
H
Spranger
Joachim
J
Lindner
Inka
I
Schreiber
Stefan
S
Rathmann
Wolfgang
W
Gohlke
Henning
H
Döring
Angela
A
Wichmann
H-Erich
HE
Schrezenmeir
Jürgen
J
Döring
Frank
F
Illig
Thomas
T
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
D019746:Intramolecular Oxidoreductases; C000605863:PTGES2 protein, human; D000071876:Prostaglandin-E Synthases