title: Influence of the alpha-adducin and ACE gene polymorphism on the progression of autosomal-dominant polycystic kidney disease.
abstract: BACKGROUND
  A significant phenotypical variability is observed in autosomal dominant polycystic kidney disease (ADPKD). The variability can not be fully explained by the genetic heterogeneity of the disease. We examined the influence of the ACE I/D polymorphism, adducin Trp460Gly polymorphism and the association of both polymorphisms on the progression of ADPKD towards end-stage renal failure (ESRF).
  
  
  METHODS
  320 ADPKD patients (pts) were analyzed, 220 pts (113 males, 107 females) with ESRF before 63 years of age, with a subgroup (rapid progressors) of 20 pts (12 males, 8 females) with ESRF before 40 years of age, 52 pts (23 males, 29 females) with ESRF later than 63 years of age (slow progressors), 48 ADPKD pts (18 males, 30 females) with mean age +/-50 years with serum creatinine <110 micromol/l (slow progressors) and 200 genetically unrelated healthy Czech subjects. DNA samples from collected blood were genotyped for the ACE I/D polymorphism and the Trp460Gly of alpha-adducin gene polymorphism.
  
  
  RESULTS
  The alpha-adducin genotypes showed no differences among the groups of slow progressors (74% Gly/Gly, 22.9% Gly/Trp and 3.1% Trp/Trp), pts with ESRF before 63 years of age (67.7% Gly/Gly, 30.5% Gly/Trp and 1.8% Trp/Trp) and rapid progressors (75% Gly/Gly, 25% Gly/Trp). The ACE genotypes did not differ among the groups of slow progressors (27.1% I/I, 44.8% I/D and 28.1% D/D), pts with ESRF before 63 years of age (23.6% I/I, 51.4% I/D and 25% D/D) and rapid progressors (20% I/I, 55% I/D and 25% D/D). The distribution did not differ from the control group. The ages of ESRF according to different genotypes did not significantly differ. We observed a significant tendency to better prognosis in Trp allele carriers for I/I genotype in comparison with Gly/Gly homozygous subjects.
  
  
  CONCLUSIONS
  The ACE and alpha-adducin polymorphisms do not play a significant role in the progression of ADPKD to ESRF.
authors.affiliation: 1st Internal Department, 1st Medical Faculty, Charles University, Prague, Czech Republic. Merta@mbox.cesnet.cz
authors.forename: M
authors.initials: M
authors.lastname: Merta
authors.forename: J
authors.initials: J
authors.lastname: Reiterová
authors.forename: J
authors.initials: J
authors.lastname: Stekrová
authors.forename: R
authors.initials: R
authors.lastname: Rysava
authors.forename: Z
authors.initials: Z
authors.lastname: Rihová
authors.forename: V
authors.initials: V
authors.lastname: Tesar
authors.forename: O
authors.initials: O
authors.lastname: Viklický
authors.forename: D
authors.initials: D
authors.lastname: Kmentova
mesh_terms: D000328:Adult; D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D010641:Phenotype; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics* / Q000503:physiopathology; D011110:Polymorphism, Genetic; D000099291:Adducins
chemical_list: D002148:Calmodulin-Binding Proteins; D007703:Peptidyl-Dipeptidase A; D000099291:Adducins