This page's own gene, PRTN3, does not just sit near the disease statistically — it encodes the exact protein the disease's own antibodies attack, and the risk variant raises how much of that protein neutrophils make.
ANCA-associated vasculitis (AAV) — including granulomatosis with polyangiitis and microscopic polyangiitis — is a rare autoimmune disease in which antineutrophil cytoplasmic antibodies (ANCAs) attack proteins inside the body's own neutrophils, causing blood vessel inflammation. This page holds 3 variants from a genetic study that traced the disease down to the exact protein its antibodies target.
A study of 1,986 AAV cases and 4,723 healthy controls, with replication and functional follow-up, found that this page's rs62132293, in PRTN3, correlated with increased PRTN3 expression in neutrophils. This is not an incidental association: PRTN3 encodes proteinase 3 (PR3), which is literally the protein many ANCAs are directed against — a risk variant that raises how much of the disease's own target protein a person's neutrophils actually produce.
The study's single largest-effect finding came from two variants at HLA-DPB1, which together with a third variant form a risk haplotype. This haplotype is associated with reduced HLA-DPB1 gene expression and HLA-DP protein levels in B cells and monocytes — and with an increased frequency of T cells reactive against that same PR3 protein. This page's second variant, rs35242582, sits in the related HLA-DQA1 gene, part of the same HLA region responsible for presenting protein fragments to the immune system.
A third position from the same study, rs7454108 in HLA-DQA2, is recorded for vasculitis with antibodies against myeloperoxidase — the other main ANCA target, with an HLA association of its own (odds ratio 2.73, 95% confidence interval 2.25 to 3.24, in a subset of 324 patients).
Combined, these findings explain a substantial share of AAV's genetic risk (a population-attributable fraction of 77% across the study's identified variants), and the study found individual loci affect the disease's two main subtypes — granulomatosis with polyangiitis and microscopic polyangiitis — differently.
2026-06-29 · New England Journal of Medicine retraction notice, PMID:33596356 (original 2021 article)
Verified directly via Europe PMC's record for the original article (PMID:33596356), which confirms a retraction notice dated 29 June 2026, plus independent corroborating coverage (RheumNow, Applied Clinical Trials Online, Vasculitis International, Rheumatology Live). The ADVOCATE trial (NEJM 2021) was the pivotal Phase 3 study behind avacopan (brand name Tavneos), an FDA-approved treatment for ANCA-associated vasculitis (the disease this page covers) -- the first time in NEJM's 200+ year history it has retracted a registrational trial that supported a regulatory approval. The trial's two academic authors, David Jayne and Peter Merkel, requested the retraction themselves after an FDA investigation revealed that personnel from the drug's original sponsor (ChemoCentryx) selected 9 patients' primary-endpoint assessments for re-adjudication after the trial's database was locked and unblinded, without the academic authors' knowledge. Five of those nine were in the avacopan treatment arm, and all five were reclassified from 'not in sustained remission' to 'sustained remission' -- changes that converted a non-superior week-52 result into the superiority finding central to the drug's approval. As of this writing, the FDA has called for market withdrawal citing the manipulated data alongside safety concerns (including reports of fatal drug-induced liver injury and vanishing bile duct syndrome), and the EMA's committee has recommended revoking its EU marketing authorization; the drug's current rights holder, Amgen, has not withdrawn it and has commissioned an independent re-adjudication. This is a drug-safety and research-integrity story, not a genetic one, and does not involve this page's own variants (PRTN3, HLA-DQA1) -- but it concerns the frontline drug for the exact disease this page covers, so this site reports it plainly rather than omitting it.
ANCA-associated vasculitis is diagnosed by ANCA antibody blood testing combined with clinical and biopsy findings — not by genotype. None of the 3 variants on this page are used by any guideline to diagnose AAV or select treatment.
The PRTN3 finding on this page is unusually direct for a genetic association: the risk variant sits in and raises expression of the exact gene encoding the protein the disease's own antibodies target. Even so, this remains population-level genetic evidence about disease mechanism, not a diagnostic test — AAV is diagnosed through ANCA antibody testing and clinical evaluation, not genotyping.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about ANCA-Associated Vasculitis comes down to these specific, well-studied positions — not a diagnosis.
PRTN3 · rs62132293
See detailed info →HLA-DQA2 · rs7454108
See detailed info →HLA-DQA1 · rs35242582
See detailed info →The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 3 of 3 linked studies with a resolved discovery ancestry.
Databases, guidelines and references
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ANCA-Associated Vasculitis. MyGeneLog™. https://www.mygenelog.com/conditions/anca-associated-vasculitis
A rare autoimmune disease in which antineutrophil cytoplasmic antibodies (ANCAs) attack proteins inside the body's own neutrophils, causing blood vessel inflammation.
A variant in PRTN3 that increases expression of proteinase 3 (PR3) in neutrophils -- PR3 is literally the protein many ANCA antibodies target, making this an unusually direct link between a genetic risk variant and the disease's own biological mechanism.
A risk haplotype at HLA-DPB1, which reduces HLA-DPB1 gene expression and increases the frequency of immune T cells reactive against proteinase 3 -- the same autoantigen the PRTN3 variant on this page also affects.
No. AAV is diagnosed by ANCA antibody blood testing and clinical evaluation. These are population-level genetic findings, not a way to predict an individual case.
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