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Balkan nephropathy.

Vladisav Stefanovic1, Draga Toncheva, Momir Polenakovic

  • 1Faculty of Medicine, University of Nis, Nis, and Serbian Academy of Sciences and Arts, Belgrade, Serbia, Department of Genetics, University of Medicine, Sofia, Bulgaria, and Macedonian Academy of Sciences and Arts, Skopje, Macedonia.

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Summary

Balkan endemic nephropathy (BN) is a kidney disease with unknown causes. Genetic mutations and epigenetic changes in BN patients offer potential biomarkers for early detection and understanding disease risk.

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Area of Science:

  • Nephrology
  • Genetics
  • Oncology

Background:

  • Balkan endemic nephropathy (BN) is a familial tubulointerstitial kidney disease linked to upper urothelial cancer.
  • Despite decades of research, the etiology of BN remains elusive, with suspected polygenic susceptibility and environmental interactions.
  • Key environmental factors implicated include Aristolochia exposure, ochratoxin A, and toxins from Pliocene lignite.

Purpose of the Study:

  • To investigate the genetic and epigenetic underpinnings of Balkan endemic nephropathy (BN).
  • To identify potential biomarkers for early detection of BN and associated urothelial cancer.
  • To explore gene-gene and gene-environment interactions contributing to BN risk.

Main Methods:

  • Exome sequencing of 22,000 genes in BN patients.
  • Analysis of gene methylation patterns (SEC61G, IL17RA, HDAC11).
  • Assessment of histone acetylation in urothelial cells from BN patients.

Main Results:

  • Mutations in CELA1, HSPG2, and KCNK5 genes were identified, affecting proteins in basement membrane, extracellular matrix, and vascular tone, crucial for angiogenesis.
  • Differential methylation was observed in SEC61G, IL17RA, and HDAC11 genes between BN patients and controls.
  • Increased acetylation of histone H3 and H4 was detected in urothelial cells of BN patients.

Conclusions:

  • Genetic markers for BN and associated urothelial cancer can be discovered through molecular research.
  • Early detection of BN-predisposing mutations and identification of susceptible individuals are feasible.
  • Further research into gene-gene and gene-environment interactions is needed to precisely determine BN risk.