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A Candidate Gene Approach to ANCA-Associated Vasculitis Reveals Links to the C3 and CTLA-4 Genes but not to the IL1-Ra And Fc gamma-RIIa Genes
Lund University, Sweden Lundby Hospital, Sweden .
Lund University, Sweden .
Lund University, Sweden .
Lund University, Sweden .
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2013 (English)In: Kidney and Blood Pressure Research, ISSN 1420-4096, E-ISSN 1423-0143, Vol. 37, no 6, 641-648 p.Article in journal (Refereed) Published
Abstract [en]

Background/Aims: The aim of the study is to search for associations between Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) and polymorphisms in the genes of four key molecules possibly involved in different pathogenic pathways; complement C3, CTLA-4, Fc gamma-RIIa and IL1-Ra. Patients and Methods: Patients with AAV (n=105) subgrouped as microscopic polyangiitis or granulomatosis with polyangiitis (Wegeners granulomatosis) and myeloperoxidase (MPO) or proteinase 3 (PR3) ANCA positive were compared to a control group of 200 blood donors. Polymorphisms in the genes were analysed with PCR amplification of DNA. Results: The diagnosis of AAV was confirmed in the 105 cases. The gene frequency of C3F was 0.27 in the PR3-ANCA subgroup (p=0.041) compared to 0,19 in the control group. The number of patients homozygous for the shortest 86 bp allele of CTLA-4 was significantly decreased in the whole group of patients (p=0.049). No differences were evident in the Fc gamma-RIIa and IL1-Ra polymorphisms when compared to controls, neither in the whole group of patients, nor in any of the sub-groups. Conclusion: The aberrant gene frequency of the C3F allele among PR3-ANCA positive patients and the findings with the CTLA-4 polymorphism indicates that complement may be involved in pathogenesis and that T-cell activation also is of importance in these diseases.

Place, publisher, year, edition, pages
Karger: Open Access Journals / S. Karger AG , 2013. Vol. 37, no 6, 641-648 p.
Keyword [en]
ANCA; Genetics; Granulomatosis with polyangiitis; Microscopic polyangiitis; Wegeners granulomatosis
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Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-103729DOI: 10.1159/000355744ISI: 000329057200013OAI: oai:DiVA.org:liu-103729DiVA: diva2:690684
Available from: 2014-01-24 Created: 2014-01-24 Last updated: 2017-12-06

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Segelmark, Mårten

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