title: Association of the genetic polymorphisms of the renin-angiotensin system and endothelial nitric oxide synthase with chronic renal transplant dysfunction.
abstract: BACKGROUND
  Chronic allograft dysfunction (CAD) is a complex phenomenon caused by underlying kidney disease and superimposed environmental and genetic factors. We investigated the association of polymorphisms in the genes for angiotensin-converting enzyme (ACE), angiotensinogen (AGT), angiotensin II receptor type 1 (ATR1) and type 2 (ATR2), and endothelial nitric oxide synthase (ENOS) with the initiation of CAD.
  
  
  METHODS
  Genotyping was performed in 125 patients who underwent renal transplantation during a 5-year period for the ACE I/D, AGT M235T, ATR1 A1166C, ATR2 C3123A, and ENOS intron 4a/b gene polymorphisms. The following information was collected for each case: date of transplantation, age and sex of donor and recipient, donor type, cold ischemia time, number of human leukocyte antigen mismatches, number of acute rejection episodes, and laboratory findings at discharge from hospital and annual rechecks. Blood pressure was measured at yearly intervals throughout follow-up.
  
  
  RESULTS
  The proportions of the genotypes were ACE II/ID/DD 12%, 33.6%, 54.4%; AGT MM/MT/TT 33%, 65.2%, 1.9%; ATR1 AA/AC/CC 68.6%, 30.7%, 0.7%; ATR2 CC/CA/AA 57.9%, 27.5%, 14.4%; and ENOS aa/ab/bb 6.4%, 22%, 71.6%, respectively. Statistical analysis of the major risk factors for the initiation of CAD showed that ACE DD genotype, cadaveric donor type, and level of proteinuria at 1 year posttransplantation were associated with poorer renal function. The graft function was not affected by AGT, ATR1, ATR2, and ENOS gene polymorphisms.
  
  
  CONCLUSIONS
  These findings suggest that the DD variant of the ACE gene polymorphism is associated with increased risk of developing CAD.
authors.affiliation: Department of Nephrology, Baskent University Faculty of Medicine, Ankara, Turkey. akcayali@hotmail.com
authors.forename: Ali
authors.initials: A
authors.lastname: Akcay
authors.forename: Siren
authors.initials: S
authors.lastname: Sezer
authors.forename: Fatma Nurhan
authors.initials: FN
authors.lastname: Ozdemir
authors.forename: Zubeyde
authors.initials: Z
authors.lastname: Arat
authors.forename: Fatma Belgin
authors.initials: FB
authors.lastname: Atac
authors.forename: Hasibe
authors.initials: H
authors.lastname: Verdi
authors.forename: Turan
authors.initials: T
authors.lastname: Colak
authors.forename: Mehmet
authors.initials: M
authors.lastname: Haberal
mesh_terms: D000328:Adult; D000808:Angiotensinogen / Q000235:genetics; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D016030:Kidney Transplantation / Q000502:physiology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics*; D012189:Retrospective Studies; D017211:Treatment Failure
chemical_list: D017931:DNA Primers; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000808:Angiotensinogen; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D007703:Peptidyl-Dipeptidase A