title: The functional Q84R polymorphism of TRIB3 gene is associated with diabetic nephropathy in Chinese type 2 diabetic patients.
abstract: Increased oxidative stress and circulating free fatty acids (FFA) has been suggested to involve in the pathogenesis of diabetic nephropathy. TRIB3 can inhibit FFA and reactive oxygen species (ROS) stimulated podocyte production of MCP-1. Smoking increases the production of reactive oxygen species, which accelerates oxidative stress under hyperglycemia. To determine whether the Q84R polymorphism (rs2295490), alone or in combination with smoking, contributes to the development of diabetic nephropathy, a case-control study was performed in 812 Chinese patients with type 2 diabetes. Among patients, 214 had diabetic nephropathy with microalbuminuria (n=156) or overt albuminuria (n=58), and 598 did not show either of these symptoms but had diabetes for ≥10 years and were not undergoing antihypertension treatment. After adjustment for confounders, TRIB3 single-nucleotide polymorphism rs2295490 was associated with DN (OR 1.318, 95% CI 1.075, 1.653, p=0.017); smoking was also an independent risk factor for diabetic nephropathy (1.42 [1.25-2.04], p<0.001). In addition, we identified possible synergistic effects; i.e., the high-risk group (smokers with the AG+GG genotype) showed 2.13 times higher risk (1.51-3.96, p<0.001) of diabetic nephropathy than the low-risk group (nonsmokers with the AA genotype) in a multiple logistic regression analysis controlled for the confounders, but no departure from additivity was found. Our results indicate that smoking and the TRIB3 G-allele is associated with an increased risk of diabetic nephropathy, which supports the hypothesis that oxidative stress contributes to the development of diabetic nephropathy.
authors.affiliation: Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute of Endocrinology and Diabetology at Fudan University, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wen
authors.affiliation: Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, Clinical Geriatric Medicine, Henan Provincial People's Hospital, Zhengzhou, China.
authors.forename: Suijun
authors.initials: S
authors.lastname: Wang
authors.affiliation: Institute of Endocrinology and Diabetology at Fudan University, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Xuanchun
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Geriatrics, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Houguang
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Fang
authors.affiliation: Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Qin
authors.affiliation: Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China. Electronic address: suqingxinhua@163.com.
authors.forename: Qing
authors.initials: Q
authors.lastname: Su
mesh_terms: D000368:Aged; D000483:Alleles; D018797:Cell Cycle Proteins / Q000235:genetics*; D002681:China; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
chemical_list: D018797:Cell Cycle Proteins; D005230:Fatty Acids, Nonesterified; D017382:Reactive Oxygen Species; D012097:Repressor Proteins; C474831:TRIB3 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: Albuminuria; Genotype; Oxidative stress; Smoking