Risk of relapse of ANCA-associated vasculitis among patients homozygous for the proteinase 3 gene Val119Ile polymorphism
Year: 2023
Type: article
Abstract: Background The frequency of proteinase 3 gene (PRTN3) polymorphisms in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is not fully characterised. We hypothesise that the presence of a PRTN3 gene polymorphism (single nucleotide polymorphism (SNP) rs351111) is relevant for clinical outcomes. Methods DNA variant calling for SNP rs351111 (chr.19:844020, c.355G>A) in PRTN3 gene assessed the allelic frequency in patients with PR3-AAV included in the Rituximab in ANCA-Associated Vasculitis trial. This was followed by RNA-seq variant calling to characterise the mRNA expression. We compared clinical outcomes between patients homozygous for PRTN3-Ile119 or PRTN3-Val119. Results Whole blood samples for DNA calling were available in 188 patients. 75 patients with PR3-AAV had the allelic variant: 62 heterozygous PRTN3-Val119Ile and 13 homozygous for PRTN3-Ile119. RNA-seq was available for 89 patients and mRNA corresponding to the allelic variant was found in 32 patients with PR3-AAV: 25 heterozygous PRTN3-Val119Ile and 7 homozygous for PRTN3-Ile119. The agreement between the DNA calling results and mRNA expression of the 86 patients analysed by both methods was 100%. We compared the clinical outcomes of 64 patients with PR3-AAV: 51 homozygous for PRTN3-Val119 and 13 homozygous for PRTN3-Ile119. The frequency of severe flares at 18 months in homozygous PRTN3-Ile119 was significantly higher when compared with homozygous PRTN3-Val119 (46.2% vs 19.6%, p=0.048). Multivariate analysis identified homozygous PR3-Ile119 as main predictor of severe relapse (HR 4.67, 95% CI 1.16 to 18.86, p=0.030). Conclusion In patients with PR3-AAV, homozygosity for PRTN3-Val119Ile polymorphism appears associated with higher frequency of severe relapse. Further studies are necessary to better understand the association of this observation with the risk of severe relapse.
Source: RMD Open
Institutions: Mayo Clinic, Universidade do Porto, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Genentech, University of Groningen, Cleveland Clinic, University of Pennsylvania, VA Boston Healthcare System, Johns Hopkins University, Hospital for Special Surgery, Duke University, Massachusetts General Hospital, University of Geneva
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,391
Funders: Mayo Clinic, Arthritis Foundation, Biogen, Biogen Idec, Mayo Foundation for Medical Education and Research, Boston University, Vasculitis Foundation, Johns Hopkins University, Juvenile Diabetes Research Foundation United Kingdom, Immune Tolerance Network, National Institutes of Health, Genentech, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Center for Research Resources
Awards: G115515487, G1167382230, G1249096266, G1346455397, G1701317796, G1830311252, G1843845992, G210009881, G2115204312, Institute for Clinical and Translational Research (UL1), G2673130173, Translational Research in Systemic Vasculitis, Immune tolerance network: liver transplantation, Development of an ANCA-Vasculitis Index of Damage (AVID), G3213106964, G3231208761, G3436481580, G3726924859, G4387359136, G4814970433, G482277048, G5029114750, G536099884, G554752038, G5577046437, G6823653762, G9000025438, G9000053194, G9000056172, G9000105478, G9000174125, G9000284116, G9000338350, Immune Tolerance Network
OpenAlex ID: W4361294786