title: Interleukin-6 gene polymorphisms correlate with the progression of nephropathy in Chinese patients with type 2 diabetes: A prospective cohort study.
abstract: OBJECTIVE
  Interleukin-6 (IL-6), an inflammatory cytokine, is considered a candidate gene possibly involved in susceptibility to nephropathy in diabetes. This study aimed to examine whether IL-6 polymorphisms predict the progression of nephropathy in a prospective Chinese cohort of patients with type 2 diabetes.
  
  
  METHODS
  A total of 568 type 2 diabetic patients with normoalbuminuria at baseline were followed up for a mean of 5.3±1.5years. Urinary albumin-to-creatinine ratio (ACR) ⩾30mg/g in two consecutive urine tests were defined as progression to diabetic nephropathy (n=143). Five polymorphisms of IL-6 gene, rs1800795, rs1800796, rs1524107, rs2069837, and rs2069840, were genotyped. Cox proportional hazard models were used to estimate hazard ratio (HR) and 95% CI of progression to diabetic nephropathy under different genetic models.
  
  
  RESULTS
  Almost all patients (99.6%) carried the rs1800795 GG homozygous genotypes. In the Cox proportional models adjusted for multiple covariates, the HR under recessive model was 2.02 for rs1800796 GG (vs. CC+CG, 95% CI: 1.08-3.75, p=0.027), 2.37 for rs2069837 GG (vs. AA+AG, 95% CI: 1.15-4.87, p=0.019), and 2.08 for rs1524107 CC (vs. TT+TC, 95% CI: 1.12-3.89, p=0.021). These associations remained significant for rs1800796 and rs1524107 after correction for multiple testing (α=0.017). Overall, our results suggest that rs1800796 GG and rs1524107 CC homozygous genotypes may confer a greater risk for development of nephropathy in type 2 diabetes.
  
  
  CONCLUSIONS
  IL-6 gene polymorphisms rs1800796 and rs1524107 may serve as predictors of progression of nephropathy in Chinese patients with type 2 diabetes.
authors: Department of Surgery, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors: Wen-Tsan
authors: WT
authors: Chang
authors: Department of Public Health and Environmental Science and Graduate Institute of Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Nutrition and Dietetics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors: Meng-Chuan
authors: MC
authors: Huang
authors: School of Public Health, The University of Queensland, Brisbane, Australia.
authors: Hsin-Fang
authors: HF
authors: Chung
authors: Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
authors: Yen-Feng
authors: YF
authors: Chiu
authors: Department of Public Health and Environmental Science and Graduate Institute of Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Pao-Shan
authors: PS
authors: Chen
authors: Department of Public Health and Environmental Science and Graduate Institute of Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Fang-Pei
authors: FP
authors: Chen
authors: Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
authors: Chun-Yi
authors: CY
authors: Lee
authors: Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University and University Hospital, Kaohsiung, Taiwan.
authors: Shyi-Jang
authors: SJ
authors: Shin
authors: Division of Nephropathy, Department of Internal Medicine, Kaohsiung Medical University and University Hospital, Kaohsiung, Taiwan.
authors: Shang-Jyh
authors: SJ
authors: Hwang
authors: Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
authors: Ya-Fang
authors: YF
authors: Huang
authors: Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan; Department of Health Services Administration, China Medical University, Taichung, Taiwan; Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan. Electronic address: cch@nhri.org.tw.
authors: Chih-Cheng
authors: CC
authors: Hsu
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D002681:China / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000235:genetics; D003928:Diabetic Nephropathies / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015994:Incidence; D015850:Interleukin-6 / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6
keywords: Diabetic nephropathy; Interleukin-6; Polymorphisms; Prospective study; Type 2 diabetes