Influence of ACE I/D gene polymorphism in the progression of renal failure in autosomal dominant polycystic kidney disease: a meta-analysis

Tiago Veiga Pereira, Ane Cláudia Fernandes Nunes, Martina Rudnicki, Ricardo Magistroni, Alberto Albertazzi, Alexandre Costa Pereira, José Eduardo Krieger

Research output: Contribution to journalArticle

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. Conclusion. 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.

Original languageEnglish
Pages (from-to)3155-3163
Number of pages9
JournalNephrology Dialysis Transplantation
Volume21
Issue number11
DOIs
Publication statusPublished - Nov 2006

Keywords

  • ACE gene polymorphism
  • ADPKD
  • Autosomal dominant polycystic kidney disease
  • Meta-analysis
  • Progression of renal failure

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

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    Pereira, T. V., Fernandes Nunes, A. C., Rudnicki, M., Magistroni, R., Albertazzi, A., Pereira, A. C., & Krieger, J. E. (2006). Influence of ACE I/D gene polymorphism in the progression of renal failure in autosomal dominant polycystic kidney disease: a meta-analysis. Nephrology Dialysis Transplantation, 21(11), 3155-3163. https://doi.org/10.1093/ndt/gfl412