title: Relationship of angiotensin I-converting enzyme (ACE) and bradykinin B2 receptor (BDKRB2) polymorphism with diabetic nephropathy.
abstract: To determine whether ACE2I/D and BDKRB23+9/-9 polymorphism causatively affect diabetic nephropathy progression RESULTS: STZ-induced metabolic disorder, as well as inflammatory responses, was significantly aggravated in ACE II-B2R4+9bp, ACE DD-B2R+9bp, or ACE DD-B2R-9bp diabetic mice but not ACE II-B2R-9bp, indicating the genetic susceptibility of ACE DD or B2R+9bp to diabetic nephropathy. Furthermore, ACE II-B2R+9bp, ACE DD-B2R+9bp, or ACE DD-B2R-9bp rather than ACE II-B2R-9bp, worsened renal performance and enhanced pathological alterations induced by STZ. Markedly elevated monocyte chemoattractant protein-1(MCP-1), podocin, osteopontin (OPN), transforming growth factor-β1 (TGF-β1), and reduced nephrin, podocin were also detected both in diabetic mice and podocytes under hyperglycemic conditions in response to ACE II-B2R+9bp, ACE DD-B2R+9bp, or ACE DD-B2R-9bp, versus ACE II-B2R-9bp. In addition, high glucose-induced mitochondrial oxidative stress and cell apoptosis were observably increased in response to ACE II-B2R+9bp, ACE DD-B2R+9bp, or ACE DD-B2R-9bp but not ACE II-B2R-9bp.
  
  
  
  We provide first evidence indicating the causation between ACE DD or B2R+9bp genotype and the increased risk for diabetic nephropathy, broadening our horizon about the role of genetic modulators in this disease.
authors.affiliation: Medical Center of the Graduate School, Nanchang University, Nanchang, China.
authors.forename: Honghong
authors.initials: H
authors.lastname: Zou
authors.affiliation: Department of Nephrology, the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of Nephrology, the First Affiliated Hospital of Nanchang University, No.17, Yongwai Street, Donghu District, Nanchang, China.
authors.forename: Jinlei
authors.initials: J
authors.lastname: Lv
authors.affiliation: Department of Nephrology, the Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Donghu District, Nanchang, China. Electronic address: gaosi_xu@126.com.
authors.forename: Gaosi
authors.initials: G
authors.lastname: Xu
mesh_terms: D000818:Animals; D003928:Diabetic Nephropathies / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism; D050199:Podocytes / Q000378:metabolism* / Q000473:pathology; D011110:Polymorphism, Genetic; D043782:Receptor, Bradykinin B2 / Q000235:genetics / Q000378:metabolism
chemical_list: D043782:Receptor, Bradykinin B2; D007703:Peptidyl-Dipeptidase A
keywords: ACE I/D polymorphism; BDKRB2 +9/−9 polymorphism; Diabetic nephropathy; Mitochondrial oxidative stress