Common polymorphisms of the PPAR-γ2 (Pro12Ala) and PGC-1α (Gly482Ser) genes are associated with the conversion from impaired glucose tolerance to type 2 diabetes in the STOP-NIDDM trial

Aim/hypothesis. We investigated the effects of the common polymorphisms in the peroxisome proliferator-activated receptor gamma2 (PPAR-gamma2; Pro12Ala) and in PPAR-gamma coactivator 1alpha ( PGC-1alpha; Gly482Ser) genes on the conversion from impaired glucose tolerance to type 2 diabetes in participants in the STOP-NIDDM trial. This trial aimed to study the effect of acarbose in the prevention of type 2 diabetes. Methods. Genotyping was performed in 770 study subjects whose DNA was available. The Gly482Ser variant in the PGC-1alpha gene was determined with the polymerase chain reaction amplification, Hpa II enzyme digestion, and gel electrophoresis. The Pro12Ala polymorphism of the PPAR-gamma2 gene was determined by the polymerase chain reaction - single-strand conformation polymorphism analysis. Results. The Pro12Pro genotype of the PPAR-gamma2 gene predicted the conversion to diabetes in women in the acarbose group ( odds ratio 2.89, 95% CI 1.20 to 6.96; p= 0.018). The 482Ser allele of the PGC-1alpha gene had a significant interaction with the mode of treatment ( p= 0.012), and in the placebo group the 482Ser allele was associated with a 1.6-fold higher risk for type 2 diabetes compared to the Gly482Gly genotype ( 95% CI 1.06 to 2.33; p= 0.023). Acarbose prevented the development of diabetes independently of the genotype of the PPAR-gamma2 gene, but only the carriers of the 482Ser allele of the PGC-1alpha gene were responsive to acarbose treatment. Conclusion/interpretation. We conclude that the Pro12Pro genotype of the PPAR-gamma2 gene and the 482Ser allele of the PGC-1alpha gene are associated with the conversion from impaired glucose tolerance to type 2 diabetes in the STOP-NIDDM trial.