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Abstract: SA-PO394

Alterations in Notch Signaling Pathway Activity and Its Potential Role in Kidney Damage in Carriers of APOL1 Risk Alleles

Session Information

• CKD: Risk Factors for Incidence and Progression - III
  November 04, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Chronic Kidney Disease (Non-Dialysis)

• 301 CKD: Risk Factors for Incidence and Progression

Authors

• Joanes, Marianinha, Boston Medical Center, Boston, Massachusetts, United States

Marianinha Joanes,



• Yang, Shi, Boston University Medical Center, Boston, Massachusetts, United States

Shi Yang,



• Andry, Chris, Boston Medical Center, Boston, Massachusetts, United States

Chris Andry,



• Gower, Adam, Boston University, Boston, Massachusetts, United States

Adam Gower,



• Henderson, Joel M., Boston University Medical Center, Boston, Massachusetts, United States

Joel M. Henderson,

Background

The association between apolipoprotein L1 (APOL1) gene variations and the increased incidence of chronic kidney disease (CKD) in individuals of African ancestry has been well established. Despite their importance, little is known about how these variants contribute to renal dysfunction, and better understanding of this mechanism could yield new diagnostic and treatment options.

Methods

To address this shortcoming, we studied kidney tissue obtained before the development of parenchymal damage in order to identify any pathway alterations that create a milieu that promotes the later development of kidney injury. We focused on glomerular changes, given the association of APOL1 variations with several glomerular disease phenotypes. Kidney samples were stratified according to APOL1 genotype, including zero risk alleles (G0G0), one risk allele (G0G1, G0G2) and two risk alleles (G1G2). Gene expression profiling was performed using Affymetrix microarrays with RNA extracted from laser capture micro-dissected glomeruli, and biological pathways that are coordinately regulated between the G0G0 and G1G2 groups were identified using Gene Set Enrichment Analysis (GSEA).

Results

Our data shows that gene sets related to the Notch signaling pathway (NSP) are significantly coordinately upregulated in the G1G2 group compared to the G0G0 group (FDR q < 0.25).

Conclusion

Given that the NSP is already implicated in other glomerular diseases, the altered NSP activity in carriers of APOL1 risk alleles may be a precursor to future disease before overt kidney injury is apparent. This also suggests that genetic variation in APOL1 may have indirect effects on other genes relevant to glomerular function.