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Angiotensinogen gene polymorphisms and progression of chronic kidney disease in ADPKD patients

Ramanathan Gnanasambandan1, Ramprasad Elumalai2, Periyasamy Soundararajan2

  • 1Department of Biomedical Sciences, Sri Ramachandra University, Chennai, India.

Clinical and Experimental Nephrology
|October 21, 2015
PubMed

Insights

Genetic variations in the angiotensinogen (AGT) gene are linked to chronic kidney disease (CKD) progression in autosomal dominant polycystic kidney disease (ADPKD). Specifically, the AGT Thr207Met polymorphism influences how quickly kidney disease worsens.

Area of Science:

  • Genetics and Molecular Biology
  • Nephrology
  • Pharmacogenomics

Background:

  • Autosomal dominant polycystic kidney disease (ADPKD) is a progressive genetic disorder leading to kidney failure.
  • The renin-angiotensin-aldosterone system (RAAS) plays a role in CKD progression, as indicated by ACE inhibitor efficacy.
  • Investigating genetic factors like angiotensinogen (AGT) single nucleotide polymorphisms (SNPs) is crucial for understanding CKD progression in ADPKD.

Purpose of the Study:

  • To investigate the association between angiotensinogen tag-single nucleotide polymorphisms (AGT tag-SNPs) and the progression of chronic kidney disease (CKD) in ADPKD patients.
  • To identify genetic modifiers of renal disease progression in ADPKD.

Main Methods:

  • Genotyping of twelve AGT tag-SNPs in 102 ADPKD patients and 106 controls using a FRET-based KASPar method.
  • Comparison of genotypes and haplotypes between ADPKD patients and controls.
  • Logistic regression analysis to assess the effect of genotypes and hypertension on CKD progression, with stratified analysis for interactions.

Main Results:

  • Two AGT polymorphisms, rs11122577 and rs4762 (Thr207Met), were significantly associated with ADPKD.
  • Univariate and multivariate analyses identified age, hypertension, family history of diabetes, and AGT rs4762 as contributors to CKD progression in ADPKD.
  • The AGT Thr207Met polymorphism was found to modify the progression of renal disease in ADPKD patients.

Conclusions:

  • The AGT Thr207Met polymorphism is significantly associated with CKD progression in ADPKD.
  • This AGT polymorphism acts as an effect modifier for renal disease progression in ADPKD.
  • Findings highlight the role of the RAAS pathway's genetic components in ADPKD pathogenesis and progression.
Abstract

Keywords:
ADPKDAGT geneCKDESRDTag-SNP

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