Pro12Ala Polymorphism in the PPARG Gene Contributes to the Development of Diabetic Nephropathy in Chinese Type 2 Diabetic Patients
- Limei Liu, MD, PHD1,
- Taishan Zheng, MD1,
- Feng Wang, MD2,
- Niansong Wang, MD, PHD2,
- Yanyan Song, MD3,
- Ming Li, MD1,
- Lifang Li, MD1,
- Jiamei Jiang, MD1 and
- Weijing Zhao, MD1
- 1Department of Endocrinology and Metabolism, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai, China;
- 2Department of Nephrology, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, China;
- 3Department of Pharmacology and Biostatistics, Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine, Shanghai, China.
- Corresponding author: Limei Liu, lmliu{at}sjtu.edu.cn.
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L.Liu and T.Z. contributed equally to this work.
Abstract
OBJECTIVE Oxidative stress is a major contributing factor in the development of diabetic nephropathy. Peroxisome proliferator–activated receptor γ heterozygous mice and Pro12Ala polymorphism in PPARG exhibited increased resistance to oxidative stress. Smoking increases the production of reactive oxygen species, which accelerates oxidative stress under hyperglycemia. To determine whether the Pro12Ala polymorphism, alone or in combination with smoking, contributes to the development of diabetic nephropathy, a case-control study was performed in 760 Chinese patients with type 2 diabetes.
RESEARCH DESIGN AND METHODS Among patients, 532 had diabetic nephropathy with microalbuminuria (n = 245) or overt albuminuria (n = 287), and 228 did not show either of these symptoms but had had diabetes for ≥10 years and were not undergoing antihypertension treatment.
RESULTS After adjustment for confounders, the Pro/Pro genotype was significantly associated with diabetic nephropathy (odds ratio 2.30 [95% CI 1.18–4.45], P = 0.014); smoking was also an independent risk factor for diabetic nephropathy (1.99 [1.08–3.68], P = 0.029). In addition, we identified possible synergistic effects; i.e., the high-risk group (smokers with the Pro/Pro genotype) showed 4.52 times higher risk (1.78–11.48, P = 0.002) of diabetic nephropathy than the low-risk group (nonsmokers with the Pro/Ala genotype) in a multiple logistic regression analysis controlled for the confounders.
CONCLUSIONS Our results indicated that the Pro/Pro genotype and smoking were significant independent risk factors for diabetic nephropathy. The possible synergistic effects of genotype and smoking may aggravate oxidative stress and contribute to the development of diabetic nephropathy.
Footnotes
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Received July 10, 2009.
- Accepted October 7, 2009.
- © 2010 by the American Diabetes Association.
