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Abstract: SA-PO628

Variant Load in Childhood Nephrotic Syndrome Is Associated With Pattern of Therapy Response

Session Information

  • Pediatric Nephrology - II
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

  • 1800 Pediatric Nephrology

Authors

  • Cason, Rachel Kate, Duke University Medical Center, Durham, North Carolina, United States
  • Chryst-Stangl, Megan, Duke University Medical Center, Durham, North Carolina, United States
  • Huggins, Kinsie, Duke University Medical Center, Durham, North Carolina, United States
  • Lane, Brandon M., Duke University Medical Center, Durham, North Carolina, United States
  • Tu, Tiffany, Duke University Medical Center, Durham, North Carolina, United States
  • Ochoa, Alejandro, Duke University Medical Center, Durham, North Carolina, United States
  • Gbadegesin, Rasheed A., Duke University Medical Center, Durham, North Carolina, United States
Background

Nephrotic syndrome (NS) is the most common glomerular disease seen in pediatric nephrology clinics. Although the etiology for most cases of NS remains unknown, several genetic loci have been associated with Steroid Sensitive NS (SSNS). It is unclear if these loci are also associated with pattern of therapy response. In the present study, we investigated the association between NS risk loci and pattern of therapy response in a large, multi-ethnic cohort of patients with NS.

Methods

We enrolled 1058 patients with childhood onset NS comprising of Steroid Resistant NS (SRNS) and SSNS (including Infrequently Relapsing [IFR] and Frequently Relapsing/Steroid Dependent [FR/SD]). Genotyping was done using TaqMan and Direct Sanger Sequencing for 10 childhood NS risk loci: HLA-DQA1 (rs1129740 & rs1071630), BTNL2 (rs9348883), HLA-DR/DQ (rs4642516 & rs3134996), Intergenic (rs9273371), CALHM6 (rs2637678), NPHS1/KIRREL (rs56117924), TNFSF15 (rs6478109), and TNFRSF11A (rs34213471). We compared the minor allele frequencies (MAF) between NS vs. controls, SRNS vs. SSNS, and IFR vs. FR/SD. Variant load analysis comparison was performed using Wilcoxen (rank sum) 2-sample test.

Results

All 10 risk loci were associated with NS compared with controls (p=0.006 to <2.2e-16). Variant load was associated with both SRNS and FR/SD (SRNS vs. SSNS p=1.98e-15 and IFR vs. FR/SD p=0.002).

Conclusion

Our study showed that genetic risk loci for childhood NS are associated with pattern of therapy response and may predict disease outcome.

Funding

  • NIDDK Support