Abstract: PO1733
Clinical Impact of PRTN3 Polymorphism in Antineutrophil Cytoplasmic Antibody (ANCA) and Similar Vasculitides
Session Information
- Glomerular Diseases: Vasculitis and TMA
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1202 Glomerular Diseases: Immunology and Inflammation
Authors
- Chen, Dhruti P., University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
- Henderson, Candace Dione, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
- Aiello, Claudia, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
- Hu, Yichun, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
- Hogan, Susan L., University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
- Blazek, Lauren N., University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
- Ciavatta, Dominic J., University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
- Falk, Ronald J., University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
Background
Genetic variants associated with ANCA vasculitis include a single-nucleotide polymorphism (SNP) at the proteinase 3 (PRTN3) locus, however the impact of this risk variant on demographics and disease characteristics has not been fully described.
Methods
401 patients with ANCA and similar vasculitidies from the Glomerular Disease Collaborative Network were genotyped for the PRTN3 SNP (rs62132293): myeloperoxidase (MPO) (n= 197), proteinase3 (PR3) (n = 170), dual positive (n=9), and seronegative (n=25). SNP homozygous (“GG”) were compared to heterozygotes (“CG”) and homozygous (“CC”). PRTN3 expression was measured by quantitative polymerase chain reaction amplification of cDNA from patient peripheral blood polymorphonuclear leukocytes during active disease. Comparisons were done using Fisher exact and Wilcoxon tests or ANOVA. Bonferroni correction and Tukey test used for multiple comparisons Cox regression was used for multivariable time to relapse and end stage kidney disease (ESKD), with hazards ratios (HR), 95% confidence intervals (CI) reported.
Results
179 CC, 181 CG and 41 GG patients with median follow-up of 4.8 years were studied. GG patients were significantly younger at disease-onset than others (FIGURE, A). There were no statistical differences in race/sex categories, ANCA seropositivity, organ involvement, or estimated glomerular filtration rate between groups. In a subset of the cohort (n=298) GG had significantly higher peak expression of PRTN3 (FIGURE, B). In the entire group, renal disease was predominant (CC 78%, CG 83%, GG 76%, p = 0.34) and the majority of the treated patients reached remission (91% CC, 88% CG and 90% GG, p=0.79). Upon remission there was no difference in time to first relapse in GG vs. others (HR 1.02, CI 0.62,1.68, p=0.94) and time to ESKD (HR 0.62, CI 0.15, 2.67, p=0.52) adjusted for age and seropositivity.
Conclusion
Disease starts at an earlier age among GG patients, with no clear impact on outcomes. Higher PRTN3expression may explain earlier disease onset.
Funding
- NIDDK Support