PPAR-γ2 and PTPRD gene polymorphisms influence type 2 diabetes patients' response to pioglitazone in China
Abstract
Qi PEI1, 2, Qiong HUANG3, Guo-ping YANG1, 4, Ying-chun ZHAO5, Ji-ye YIN1, Min SONG4, Yi ZHENG1, Zhao-hui MO6, *, Hong-hao ZHOU1, Zhao-qian LIU1, *
1Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China; 2Department of Pharmacy, Third Xiangya Hospital, Central South University, Changsha 410013, China; 3Institute of Clinical Pharmacology, Anhui Medical University, Hefei 230032, China; 4Center of Clinical Pharmacology, Third Xiangya Hospital, Central South University, Changsha 410013, China; 5Osteoporosis Research Center, Creighton University, Omaha, NE 68131, USA; 6Department of Endocrinology, Third Xiangya Hospital, Central South University, Changsha 410013, China
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.
Keywords: pioglitazone; type 2 diabetes; PPAR-γ2 rs1801282; PTPRD rs17584499; genetic polymorphisms; Chinese Han population
This work was supported by the National High-tech R&D Program of China (863 Program) (2012AA02A517), National Natural Science Foundation of China (81173129 and 81202596), Program for Changjiang Scholars and Innovative Research Team in University (IRT0946).
* To whom correspondence should be addressed.
E-mail liuzhaoqian63@126.com (Zhao-qian LIU); easd04mzh@126.com (Zhao-hui MO)
Received 2012-07-27 Accepted 2012-09-18
Keywords:
1Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China; 2Department of Pharmacy, Third Xiangya Hospital, Central South University, Changsha 410013, China; 3Institute of Clinical Pharmacology, Anhui Medical University, Hefei 230032, China; 4Center of Clinical Pharmacology, Third Xiangya Hospital, Central South University, Changsha 410013, China; 5Osteoporosis Research Center, Creighton University, Omaha, NE 68131, USA; 6Department of Endocrinology, Third Xiangya Hospital, Central South University, Changsha 410013, China
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.
Keywords: pioglitazone; type 2 diabetes; PPAR-γ2 rs1801282; PTPRD rs17584499; genetic polymorphisms; Chinese Han population
This work was supported by the National High-tech R&D Program of China (863 Program) (2012AA02A517), National Natural Science Foundation of China (81173129 and 81202596), Program for Changjiang Scholars and Innovative Research Team in University (IRT0946).
* To whom correspondence should be addressed.
E-mail liuzhaoqian63@126.com (Zhao-qian LIU); easd04mzh@126.com (Zhao-hui MO)
Received 2012-07-27 Accepted 2012-09-18