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Abstract: FR-PO630

Pathogenic Genes in the Mesoamerican ESRD Population

Session Information

Category: Genetic Diseases of the Kidneys

  • 1202 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Kore, Shruti, Westchester Medical Center, Valhalla, New York, United States
  • Obayomi, Mobolaji Ayodeji, Westchester Medical Center, Valhalla, New York, United States
  • Clark, Dinah, Natera Inc, Austin, Texas, United States
  • Wade, Heather, Natera Inc, Austin, Texas, United States
  • Coritsidis, George N., Westchester Medical Center, Valhalla, New York, United States
Background

Dialysis clinics in the New York area treat a large population of immigrants originating from Central and Northern South America. Many do not have an etiology for ESRD, which may result from Mesoamerican (MA) Nephropathy, a pathology not well understood. This study assesses if there are underlying diseases due to genetic variances that predispose these patients to ESRD.

Methods

MA subjects were recruited prospectively from Atlantic Dialysis Management Services units in New York City and Dialysis Clinic Inc. from Westchester Medical Center, along with Non-Mesoamerican subjects (n-MA). Saliva swabs were acquired and processed via Renasight genetic kits. 385 genes were assessed for pathogenic or likely pathogenic variants.

Results

228 subjects were recruited, of which 123 were MA. 11% of MAs were found to have 23 pathogenic or likely pathogenic variants of positive genes. Of these 23 cases, the most common variants were identified in genes associated with Alport Syndrome (COL4A3 and COL4A4) at a frequency of 26% (6/23). The variants in genes associated with Polycystic Kidney Disease (PKD) (PKD1 and PKD2) also had a frequency of 22% (5/23). Of the 105 n-MA subjects, 20% of them were found to have 39 pathogenic or likely pathogenic variants of positive genes. The frequency of pathogenic variants of genes encoding for Alport Syndrome is 10%, and the frequency of PKD is 8%. The frequency of pathogenic variants of genes encoding for Alport Syndrome is 10% (4/39), and the frequency of PKD is 8% (3/39). The incidence of the APOL1 risk allele in the n-MA population was 28% (11/39), compared to 4% (1/23) in the MA population.

Conclusion

The frequency of genes related to Alport’s Syndrome and PKD were increased in MAs. The higher frequency of APOL1 risk alleles in the n-MA contributes to a higher incidence of variants of positive genes, but it is unclear if this led to an underlying genetic cause of kidney disease. Although pathogenic variants were found, their presence does not clearly point to genetic etiologies for MA Nephropathy.

Left: n-MA pathogenic variants
Right: MA pathogenic variants

Funding

  • Commercial Support – Natera