title: Endothelin-1 gene polymorphisms and diabetic kidney disease in patients with type 2 diabetes mellitus.
abstract: OBJECTIVE
  Diabetic kidney disease (DKD) is the leading cause of end stage renal disease worldwide and is associated with increased cardiovascular mortality. The endothelin system has been implicated in the pathogenesis of arterial hypertension and renal dysfunction. In the present study, the association of DKD with polymorphisms in ET-1 (EDN1) and ETRA (EDNRA) genes was analyzed in patients with type 2 diabetes mellitus (T2DM).
  
  
  METHODS
  A case-control study was conducted in 548 white T2DM patients. Patients with proteinuria or on dialysis were considered cases and patients with normoalbuminuria were considered controls. Two polymorphisms in the EDN1 gene (rs1800541 and rs57072783) and five in EDNRA gene (rs6842241; rs4835083; rs4639051; rs5333 and rs5343) were genotyped and haplotype analyses were performed.
  
  
  RESULTS
  The presence of rs57072783 T allele (TT/TG vs. GG) or rs1800541 G allele (GG/GT vs. TT) protected against DKD (OR = 0.69, 95 % CI 0.48-0.99, P = 0.049; and OR = 0.60, 95 % CI 0.41-0.88, P = 0.009, respectively). However in multivariate analyses, only the rs1800541 G allele remained independently associated with DKD (P = 0.046).
  
  
  CONCLUSIONS
  The present study shows that ET-1 could be involved in the pathogenesis of DKD in patients with T2DM.
authors.affiliation: Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Claudete M
authors.initials: CM
authors.lastname: Zanatta
authors.affiliation: Federal University of Rio Grande do Sul, Porto Alegre, Brazil ; Endocrine Division, Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, RS Brazil.
authors.forename: Daisy
authors.initials: D
authors.lastname: Crispim
authors.affiliation: Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Denise A
authors.initials: DA
authors.lastname: Sortica
authors.affiliation: Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Lucas P
authors.initials: LP
authors.lastname: Klassmann
authors.affiliation: Federal University of Rio Grande do Sul, Porto Alegre, Brazil ; Endocrine Division, Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, RS Brazil.
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Gross
authors.affiliation: Federal University of Rio Grande do Sul, Porto Alegre, Brazil ; Endocrine Division, Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, RS Brazil.
authors.forename: Fernando
authors.initials: F
authors.lastname: Gerchman
authors.affiliation: Federal University of Rio Grande do Sul, Porto Alegre, Brazil ; Endocrine Division, Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, RS Brazil.
authors.forename: Luís H
authors.initials: LH
authors.lastname: Canani
keywords: Diabetes mellitus type 2; Diabetic kidney disease; Endothelin-1