dc.contributor.author | Dahlqvist, Johanna | |
dc.contributor.author | Ekman, Diana | |
dc.contributor.author | Sennblad, Bengt | |
dc.contributor.author | Kozyrev, Sergey V. | |
dc.contributor.author | Nordin, Jessika | |
dc.contributor.author | Karlsson, Åsa | |
dc.contributor.author | Meadows, Jennifer R. S. | |
dc.contributor.author | Hellbacher, Erik | |
dc.contributor.author | Rantapää-Dahlqvist, Solbritt | |
dc.contributor.author | Berglin, Ewa | |
dc.contributor.author | Stegmayr, Bernd | |
dc.contributor.author | Haslund, Bo | |
dc.contributor.author | Palm, Øyvind | |
dc.contributor.author | Haukeland, Hilde | |
dc.contributor.author | Gunnarsson, Iva | |
dc.contributor.author | Bruchfeld, Annette | |
dc.contributor.author | Segelmark, Mårten | |
dc.contributor.author | Ohlsson, Sophie | |
dc.contributor.author | Mohammad, Aladdin J. | |
dc.contributor.author | Svärd, Anna Jessica | |
dc.contributor.author | Pullerits, Rille | |
dc.contributor.author | Herlitz, Hans | |
dc.contributor.author | Söderbergh, Annika | |
dc.contributor.author | Pielberg, Gerli Rosengren | |
dc.contributor.author | Rosenberg, Lina Hultin | |
dc.contributor.author | Bianchi, Matteo | |
dc.contributor.author | Muren, Eva | |
dc.contributor.author | Omdal, Roald | |
dc.contributor.author | Jonsson, Roland | |
dc.contributor.author | Eloranta, Maija-Leena | |
dc.contributor.author | Rönnblom, Lars | |
dc.contributor.author | Söderkvist, Peter | |
dc.contributor.author | Knight, Ann | |
dc.contributor.author | Eriksson, Per | |
dc.contributor.author | Lindblad-Toh, Kerstin | |
dc.date.accessioned | 2022-04-22T08:06:14Z | |
dc.date.available | 2022-04-22T08:06:14Z | |
dc.date.created | 2022-03-02T11:00:23Z | |
dc.date.issued | 2021 | |
dc.identifier.issn | 1462-0324 | |
dc.identifier.uri | https://hdl.handle.net/11250/2992154 | |
dc.description.abstract | Objective
To identify and characterize genetic loci associated with the risk of developing ANCA-associated vasculitides (AAV).
Methods
Genetic association analyses were performed after Illumina sequencing of 1853 genes and subsequent replication with genotyping of selected single nucleotide polymorphisms in a total cohort of 1110 Scandinavian cases with granulomatosis with polyangiitis or microscopic polyangiitis, and 1589 controls. A novel AAV-associated single nucleotide polymorphism was analysed for allele-specific effects on gene expression using luciferase reporter assay.
Results
PR3-ANCA+ AAV was significantly associated with two independent loci in the HLA-DPB1/HLA-DPA1 region [rs1042335, P = 6.3 × 10−61, odds ratio (OR) 0.10; rs9277341, P = 1.5 × 10−44, OR 0.22] and with rs28929474 in the SERPINA1 gene (P = 2.7 × 10−10, OR 2.9). MPO-ANCA+ AAV was significantly associated with the HLA-DQB1/HLA-DQA2 locus (rs9274619, P = 5.4 × 10−25, OR 3.7) and with a rare variant in the BACH2 gene (rs78275221, P = 7.9 × 10−7, OR 3.0), the latter a novel susceptibility locus for MPO-ANCA+ granulomatosis with polyangiitis/microscopic polyangiitis. The rs78275221-A risk allele reduced luciferase gene expression in endothelial cells, specifically, as compared with the non-risk allele.
Conclusion
We identified a novel susceptibility locus for MPO-ANCA+ AAV and propose that the associated variant is of mechanistic importance, exerting a regulatory function on gene expression in specific cell types. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | Oxford University Press | en_US |
dc.rights | Navngivelse-Ikkekommersiell 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/4.0/deed.no | * |
dc.title | Identification and functional characterization of a novel susceptibility locus for small vessel vasculitis with MPO-ANCA | en_US |
dc.type | Journal article | en_US |
dc.type | Peer reviewed | en_US |
dc.description.version | publishedVersion | en_US |
dc.rights.holder | Copyright 2021 The Author(s) | en_US |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.doi | 10.1093/rheumatology/keab912 | |
dc.identifier.cristin | 2006924 | |
dc.source.journal | Rheumatology | en_US |
dc.identifier.citation | Rheumatology. 2021 | en_US |