ArticleRheumatology (Oxford, England)2023
Stratified genetic analysis reveals sex differences in MPO-ANCA-associated vasculitis.
Article in Rheumatology (Oxford, England), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed, 9 citations in OpenAlex.
- Genetic burden across core genes of the PI3K-AKT-mTOR pathway is associated with susceptibility to microscopic polyangiitis: a Chinese cohort study.Frontiers in immunology · 2026Article
- In-Depth Analysis of Disease Manifestations in Antineutrophil Cytoplasmic Antibody-Associated Vasculitides Identifies Distinct Clinical Phenotypes.ACR open rheumatology · 2025Article
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25 authors at 15 institutions in 5 countries.
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No grant is acknowledged in the PubMed record.
Abstract
objectiveTo identify and genetically characterize subgroups of patients with ANCA-associated vasculitides (AAV) based on sex and ANCA subtype.
methodsA previously established SNP dataset derived from DNA sequencing of 1853 genes and genotyping of 1088 Scandinavian cases with AAV and 1589 controls was stratified for sex and ANCA subtype and analysed for association with five top AAV SNPs. rs9274619, a lead variant at the HLA-DQB1/HLA-DQA2 locus previously associated with AAV positive for myeloperoxidase (MPO)-ANCA, was analysed for association with the cumulative disease involvement of ten different organ systems.
resultsrs9274619 showed a significantly stronger association to MPO-ANCA-positive females than males [P = 2.0 × 10-4, OR = 2.3 (95% CI 1.5, 3.5)], whereas proteinase 3 (PR3)-ANCA-associated variants rs1042335, rs9277341 (HLA-DPB1/A1) and rs28929474 (SERPINA1) were equally associated with females and males with PR3-ANCA. In MPO-ANCA-positive cases, carriers of the rs9274619 risk allele were more prone to disease engagement of eyes [P = 0.021, OR = 11 (95% CI 2.2, 205)] but less prone to pulmonary involvement [P = 0.026, OR = 0.52 (95% CI 0.30, 0.92)]. Moreover, AAV with both MPO-ANCA and PR3-ANCA was associated with the PR3-ANCA lead SNP rs1042335 [P = 0.0015, OR = 0.091 (95% CI 0.0022, 0.55)] but not with rs9274619.
conclusionsFemales and males with MPO-ANCA-positive AAV differ in genetic predisposition to disease, suggesting at least partially distinct disease mechanisms between the sexes. Double ANCA-positive AAV cases are genetically similar to PR3-ANCA-positive cases, providing clues to the clinical follow-up and treatment of these patients.
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