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DOI: 10.2337/db05-1629
© 2006 by the American Diabetes Association
Brief Genetics Reports |
Single Nucleotide Polymorphisms of PPARD in Combination With the Gly482Ser Substitution of PGC-1A and the Pro12Ala Substitution of PPARG2 Predict the Conversion From Impaired Glucose Tolerance to Type 2 Diabetes
The STOP-NIDDM Trial
1
1 Department of Medicine, University of Kuopio, Kuopio, Finland
2 Research Centre, Centre Hospitalier de l’Université de Montréal, Hôtel-Dieu, Department of Medicine, University of Montreal, Quebec, Canada
Address correspondence and reprint requests to Markku Laakso, MD, Academy Professor, Department of Medicine, University of Kuopio, 70210 Kuopio, Finland. E-mail: markku.laakso{at}kuh.fi
Abbreviations:
FFA, free fatty acid; IGT, impaired glucose tolerance; LD, linkage disequilibrium; PGC-1
, PPAR-
coactivator 1; PPAR, peroxisome proliferator–activated receptor; SNP, single nucleotide polymorphism
Peroxisome proliferator–activated receptor (PPAR)-
regulates fatty acid oxidation and improves insulin sensitivity. We screened six single nucleotide polymorphisms (SNPs) of the PPAR- gene (PPARD) for an association with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes in 769 subjects participating in the STOP-NIDDM trial. A 2.7-fold increase in the risk of diabetes was observed in female carriers of the C allele of rs6902123 (95% CI 1.44–5.30; adjusted P = 0.002). In the placebo group, subjects possessing both the 482Ser allele of the PPAR- coactivator-1 gene (PGC-1A) and the rare allele of two SNPs of PPARD (rs6902123 and rs3734254) had up to 2.5-fold increased risk for diabetes. Furthermore, women carrying the C allele of rs6902123 of PPARD and the Pro12Pro genotype of the PPAR-2 gene (PPARG2) had a 3.9-fold (95% CI 1.79–8.63; P = 0.001)-higher risk for diabetes than women with protective genotypes. Expression levels of PPAR- in subcutaneous adipose tissue of 87 offspring of Finnish patients with type 2 diabetes did not differ among the genotype groups of SNPs of PPARD. We conclude that SNPs in PPARD modify the conversion from IGT to type 2 diabetes, particularly in combination with the SNPs of PGC-1A and PPARG2.
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