Effects of Pro12Ala polymorphism of peroxisome proliferator-activated receptor γ2 gene on rosiglitazone response in type 2 diabetes

Objective: The aim of this study was to examine the effects of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor (PPAR) gamma 2 gene on the response to rosiglitazone in patients with type 2 diabetes mellitus. Methods: A total of 198 patients with type 2 diabetes mellitus were treated with rosiglitazone (4 mg/d) for 12 weeks without a change in previous medications. All patients were genotyped for the PPAR gamma 2 Pro12A1a polymorphism. Results: The Ala12 allele frequency was 0.04. Of the 198 patients, 183 had the Pro12Pro genotype and 15 had the Pro12A1a genotype. The Ala12A1a genotype was not observed. The decrease in fasting plasma glucose level was significantly greater in subjects with the Ala12 allele than in those without the allele (50.6 +/- 27.8 mg/dL versus 24.3 +/- 41.9 mg/dL, P = .026). In addition, the decrease in hemoglobin A(1c) level was significantly greater in subjects with the Ala12 allele than in those without the allele (1.41% +/- 1.47% versus 0.57% +/- 1.16%, P = .015). There was a significant difference in the response rate to rosiglitazone treatment between the Pro12Pro group and the Pro12A1a variant group (43.72% versus 86.67%, P = .002). Conclusion: Patients with the Pro12A1a genotype in the PPAR gamma 2 gene had a better therapeutic response to rosiglitazone than did patients with the Pro12Pro genotype. The genetic variations in the PPAR gamma 2 gene can affect the response to rosiglitazone treatment in patients with type 2 diabetes mellitus.