title: Nodular glomerulosclerosis and renin angiotensin system in Chinese patients with type 2 diabetes.
abstract: BACKGROUND
  Diabetic nephropathy (DN) is a multifactorial and polygenic disease with nodular glomerulosclerosis (NGS) pathognomonic for diabetes and hypertension. Patients with type 2 diabetes and hypertension have characteristic renin-angiotensin system (RAS) gene polymorphisms.
  
  
  RESULTS
  In this retrospective cohort study, we correlated the presence of NGS with renal function, angiotensin-converting enzyme (ACE) genotypes (DD, DI, and II), angiotensinogen (AGT) genotypes (MM, MT, and TT) and immunohistochemical staining characteristics of RAS components in 847 patients and 172 consecutive autopsy cases with type 2 diabetes. T allele of AGT was associated with macroalbuminuria (P = 0.040). Multitude regression analysis revealed ACE insertion (I)/deletion (D) polymorphism as an independent determinant for estimated glomerular filtration rate (eGFR) less than 60 mL min(-1)·1.73 m(-2) (DD carriers: odds ratio [OR] = 3.46, 95% confidence interval [CI] = 1.08-11.07; DI carriers: OR = 3.51, 95% CI = 1.63-7.56). A significant association between NGS and eGFR less than 60 mL min(-1)·1.73 m(-2) also persisted after adjusting for nonlinear relationship (P < 0.001). In NGS patients, immunoreactivity of angiotensin I converting enzyme 2 (ACE2) significantly decreased in glomeruli with mesangial nodules compared with glomeruli without the mesangial nodules.
  
  
  CONCLUSIONS
  These data suggest associations of ACE D allele with glomerular filtration impairment, and NGS with glomerular ACE2 down-regulation and reduced glomerular filtration in Chinese patients with type 2 diabetes.
authors.affiliation: Institute of Basic Medical Sciences, Guilin Medical University, Guilin 541004, China; Center for Diabetic Systems Medicine, Guangxi Key Laboratory of Excellence, Guilin Medical University, Guilin 541004, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Institute of Basic Medical Sciences, Guilin Medical University, Guilin 541004, China; Center for Diabetic Systems Medicine, Guangxi Key Laboratory of Excellence, Guilin Medical University, Guilin 541004, China.
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Center for Diabetic Systems Medicine, Guangxi Key Laboratory of Excellence, Guilin Medical University, Guilin 541004, China.
authors.forename: Xinnan
authors.initials: X
authors.lastname: Song
authors.affiliation: Institute of Basic Medical Sciences, Guilin Medical University, Guilin 541004, China; Center for Diabetic Systems Medicine, Guangxi Key Laboratory of Excellence, Guilin Medical University, Guilin 541004, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zou
authors.affiliation: Institute of Basic Medical Sciences, Guilin Medical University, Guilin 541004, China; Center for Diabetic Systems Medicine, Guangxi Key Laboratory of Excellence, Guilin Medical University, Guilin 541004, China.
authors.forename: Weijie
authors.initials: W
authors.lastname: Wu
authors.affiliation: Institute of Basic Medical Sciences, Guilin Medical University, Guilin 541004, China; Center for Diabetic Systems Medicine, Guangxi Key Laboratory of Excellence, Guilin Medical University, Guilin 541004, China.
authors.forename: Yanchao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Basic Medical Sciences, Guilin Medical University, Guilin 541004, China; Center for Diabetic Systems Medicine, Guangxi Key Laboratory of Excellence, Guilin Medical University, Guilin 541004, China.
authors.forename: Bingjie
authors.initials: B
authors.lastname: Lin
authors.affiliation: Center for Diabetic Systems Medicine, Guangxi Key Laboratory of Excellence, Guilin Medical University, Guilin 541004, China; Endocrinology and Toxicology Laboratory, Department of Biology, Hong Kong Baptist University, Hong Kong SAR 999077, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.affiliation: Metabolic Syndrome Research Center, The Second Xiangya Hospital, Central South University, Changsha 410000, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Hu
authors.affiliation: Institute of Basic Medical Sciences, Guilin Medical University, Guilin 541004, China; Center for Diabetic Systems Medicine, Guangxi Key Laboratory of Excellence, Guilin Medical University, Guilin 541004, China. Electronic address: zhaohailu9@126.com.
authors.forename: Hailu
authors.initials: H
authors.lastname: Zhao
mesh_terms: D044466:Asian People / Q000235:genetics; D002681:China; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics* / Q000473:pathology; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D005919:Glomerular Filtration Rate / Q000235:genetics; D006801:Humans; D006973:Hypertension / Q000150:complications; D016130:Immunophenotyping; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011507:Proteinuria / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics* / Q000276:immunology; D012189:Retrospective Studies
chemical_list: D008055:Lipids
keywords: Angiotensin I converting enzyme 2; Hypertension; Nodular glomerulosclerosis; Renin-angiotensin system; Type 2 diabetes