PPAR-γ2 and PTPRD gene polymorphisms influence type 2 diabetes patients' response to pioglitazone in China

Abstract

Aim: To investigate the influence of peroxisome proliferator-activated receptor γ2 (PPAR-γ2) gene polymorphism rs1801282 and protein tyrosine phosphatase receptor type D (PTPRD) gene polymorphism rs17584499 on the occurrence of type 2 diabetes and pioglitazone efficacy in a Chinese Han population. Methods: One hundred ninety seven type 2 diabetes patients and 212 healthy controls were enrolled. Among them, 67 type 2 diabetes patients were administered pioglitazone (30 mg/d, po) for 3 months. All the subjects were genotyped for genetic variants in PPAR-γ2 and PTPRD using MALDI-TOF mass spectrometry. Fasting plasma glucose, postprandial plasma glucose, glycated hemoglobin, serum triglyceride, total cholesterol, low-density and high-density lipoprotein-cholesterol were determined. Results: The PPAR-γ2 gene rs1801282 polymorphism was significantly associated with type 2 diabetes susceptibility (OR=0.515, 95% CI 0.268-0.990) and the PTPRD gene rs17584499 polymorphism was also significantly associated with type 2 diabetes (OR=1.984, 95% CI 1.135-3.469) in a dominant model adjusted for age, gender and BMI. After pioglitazone treatment for 3 months, the type 2 diabetes patients with PPAR-γ2 rs1801282 CG genotypes significantly showed higher differential values of postprandial plasma glucose and serum triglyceride compared with those with rs1801282 CC genotype. The patients with PTPRD rs17584499 CT+TT genotypes showed significantly lower differential value of postprandial plasma glucose compared to those with rs17584499 CC genotype. Conclusion: Diabetes risk alleles in PPAR-γ2 (rs1801282) and PTPRD (rs17584499) are associated with pioglitazone therapeutic efficacy.

Pharmacogenomics and Pharmacogenetics of Thiazolidinediones: Role in Diabetes and Cardiovascular Risk Factors

“…This study also indicated that P12A mutation might also be linked to adipogenesis [66]. Furthermore, various research groups have shown that biological variability linked with the glucose-lowering effect of pioglitazone is also partly ascribed to the polymorphism associated with PPARG gene [67–69]. The PTPRD SNP rs17584499, located in intron 10, has been identified in Chinese populations as another important factor leading to pharmacodynamic variability in the glucose-lowering effect of pioglitazone [69].…”

“…Furthermore, various research groups have shown that biological variability linked with the glucose-lowering effect of pioglitazone is also partly ascribed to the polymorphism associated with PPARG gene [67–69]. The PTPRD SNP rs17584499, located in intron 10, has been identified in Chinese populations as another important factor leading to pharmacodynamic variability in the glucose-lowering effect of pioglitazone [69]. A substantial alteration of pioglitazone-induced reduction in HbAlc was observed in ADIPOQ C-11377G genotype and ADIPOR2 G795A genotype in Chinese and Iranian T2D populations [43,70].…”

Patient profiling in diabetes and role of canagliflozin

“…In 197 Chinese Han T2DM patients of whom 67 patients were given pioglitazone (30 mg/day for 12 weeks), those patients with PPARγ2 gene polymorphism rs1801282 CG showed significantly higher levels of PPPG and serum triglyceride compared with those with rs1801282 CC genotype 28. In patients with protein tyrosine phosphatase receptor type D gene polymorphism rs17584499, the CC genotype had better PPPG levels compared with CT + TT genotypes 28.…”

“…In patients with protein tyrosine phosphatase receptor type D gene polymorphism rs17584499, the CC genotype had better PPPG levels compared with CT + TT genotypes 28. In 241 Chinese patients with T2DM of whom 41 patients were given rosiglitazone (4 mg daily for 12 weeks), the presence of the SNPs Thr394Thr and Gly482Ser of the PPARγ coactivator-1 gene increased the therapeutic efficacy of rosiglitazone when compared to controls 29…”

Variants of Insulin-Signaling Inhibitor Genes in Type 2 Diabetes and Related Metabolic Abnormalities

“…Interestingly, in this study rs17584499 was found to be associated also with pioglitazone therapeutic efficacy. In fact, patients with rs17584499 CT+TT genotypes showed significantly lower differential value of postprandial plasma glucose compared to those with CC genotype after pioglitazone treatment for 3 months [58]. …”