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Abstract: TH-PO367

Genetic Variants and Phenotypic Heterogeneity in Autosomal Dominant Polycystic Kidney Disease

Session Information

Category: Genetic Diseases of the Kidneys

  • 1101 Genetic Diseases of the Kidneys: Cystic

Authors

  • Vespa, Marta, IRCCS Ospedale San Raffaele, Milano, Lombardia, Italy
  • Sciarrone Alibrandi, Maria Teresa, IRCCS Ospedale San Raffaele, Milano, Lombardia, Italy
  • Joli, Giancarlo, IRCCS Ospedale San Raffaele, Milano, Lombardia, Italy
  • Bucci, Romina, IRCCS Ospedale San Raffaele, Milano, Lombardia, Italy
  • Catania, Martina, IRCCS Ospedale San Raffaele, Milano, Lombardia, Italy
  • De Rosa, Liliana Italia, IRCCS Ospedale San Raffaele, Milano, Lombardia, Italy
  • Citterio, Lorena, IRCCS Ospedale San Raffaele, Milano, Lombardia, Italy
  • Vergani, Maria Vittoria, IRCCS Ospedale San Raffaele, Milano, Lombardia, Italy
  • Paolisi, Michele, IRCCS Ospedale San Raffaele, Milano, Lombardia, Italy
  • Bianca, Pierpaolo, IRCCS Ospedale San Raffaele, Milano, Lombardia, Italy
  • Vezzoli, Giuseppe, IRCCS Ospedale San Raffaele, Milano, Lombardia, Italy
  • Manunta, Paolo, IRCCS Ospedale San Raffaele, Milano, Lombardia, Italy
Background

Adpkd is the most common genetic renal disease usually caused by the mutation of the genes PKD1-PKD2. The main feature is bilateral renal enlargement with progressive loss of kidney function. One of the most typical aspect of this disease is the intra-interfamiliar phenotypical variability.

Methods

We led an observational retrospective cross sectional study on 191 PKD pts to evaluate the phenotypical variability based on causal genes and modifier genes, that can influence clinical features: hypertension, sodium sensitivity etc.

Results

Among the polymorphisms, rs4961, rs3731566, rs4293393, rs10900555 seem to have influence on renal phenotype. We observed different disease trend outcomes between wild type patients and those with the rs4961 (ADD1) and
rs4293393 (UMOD) variants. In our cohort rs3731566 (ADD3) significantly correlates with a worse kidney function and an early ESRD. On the other hand, rs10900555 (REN) correlates with ESRD before age 60. By analyzing the interactions between the potential modifier genes and the causal genes, we found that the most severe mutation, the PKD1 truncating one, seems to delete the effects of ADD1 and UMOD, something that did not happen with ADD3, which AA genotypic presence correlates with a worse outcome, despite the kind of PKD1 mutation. Our hypothesis is that, despite the phenotypic effect of PKD1T, we were still able to find modifier genes capable to generate a significant change in phenotype.

Conclusion

Our results lead the way to further analysis, specifically regarding the pharmacogenomics aspect and the functional interactions among these proteins