title: Influence of ACE I/D gene polymorphism in the progression of renal failure in autosomal dominant polycystic kidney disease: a meta-analysis.
abstract: BACKGROUND
  Autosomal dominant polycystic kidney disease (ADPKD) is a renal disease characterized by an important variability in clinical course, which cannot be fully explained by the genetic heterogeneity of the disease. Although the role for the angiotensin I-converting enzyme (ACE) insertion/deletion (I/D) polymorphism as a modifier factor in ADPKD renal deterioration has been suggested, direct evidence from genetic association studies remain inconclusive. To provide a more robust estimate of the putative effect of the ACE I/D polymorphism on the renal progression in ADPKD, we performed a meta-analysis pooling data from all relevant studies in which the role of the ACE I/D variant in ADPKD clinical features was evaluated.
  
  
  METHODS
  We applied a random-effects model to combine odds ratio and 95% confidence intervals. Q-statistic was used to evaluate the homogeneity, and both Egger's and Begg-Mazumdar tests were used to assess publication bias.
  
  
  RESULTS
  Altogether, three distinct meta-analyses were generated using data from 13 studies. Despite the absence of publication bias and the presence of homogeneity among study results, the DD genotype failed to show an influence on risk of end-stage renal disease (ESRD), mean age at ESRD or risk of hypertension in ADPKD patients when compared with I-allele carriers (DD vs ID+II). Likewise, meta-analyses carried out separately for Caucasian and Asian studies showed no indication of an association between the DD genotype and a faster renal deterioration in ADPKD.
  
  
  CONCLUSIONS
  These findings do not support the hypothesis that the enhanced ACE activity associated with the D allele might promote a significantly worse prognosis in patients with ADPKD.
authors.affiliation: Department of Biochemistry and Molecular Biology, Federal University of São Paulo, Brazil. t27026t@yahoo.com.br
authors.forename: Tiago Veiga
authors.initials: TV
authors.lastname: Pereira
authors.forename: Ane Cláudia Fernandes
authors.initials: AC
authors.lastname: Nunes
authors.forename: Martina
authors.initials: M
authors.lastname: Rudnicki
authors.forename: Ricardo
authors.initials: R
authors.lastname: Magistroni
authors.forename: Alberto
authors.initials: A
authors.lastname: Albertazzi
authors.forename: Alexandre Costa
authors.initials: AC
authors.lastname: Pereira
authors.forename: José Eduardo
authors.initials: JE
authors.lastname: Krieger
mesh_terms: D000375:Aging / Q000235:genetics; D000483:Alleles; D001483:Base Sequence; D018450:Disease Progression; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000201:enzymology / Q000235:genetics; D007676:Kidney Failure, Chronic / Q000201:enzymology* / Q000235:genetics* / Q000503:physiopathology; D008957:Models, Genetic; D016254:Mutagenesis, Insertional; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D016891:Polycystic Kidney, Autosomal Dominant / Q000201:enzymology* / Q000235:genetics* / Q000503:physiopathology; D011110:Polymorphism, Genetic / Q000502:physiology; D011379:Prognosis; D012307:Risk Factors
chemical_list: D007703:Peptidyl-Dipeptidase A