Genetics of toll like receptor 9 in ANCA associated vasculitides
| Autor: | Julia U Holle, Gunter Assmann, Wolfgang L. Gross, C A Husmann, S Mueller, Benjamin Wilde, J. W. Cohen Tervaert, Jörg T. Epplen, Lorraine Harper, F Moosig, Stefan Wieczorek |
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| Přispěvatelé: | Interne Geneeskunde, Faculteit FHML Centraal, RS: CARIM - R3 - Vascular biology, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience |
| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Interleukin-23 receptor Genotype Immunology Medizin Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide Linkage Disequilibrium General Biochemistry Genetics and Molecular Biology Rheumatology Proteinase 3 medicine Humans Immunology and Allergy Genetic Predisposition to Disease Interleukin 6 Genetics Haplotype medicine.disease Case-Control Studies Toll-Like Receptor 9 biology.protein Female Gene polymorphism Granulomatosis with polyangiitis Microscopic polyangiitis |
| Zdroj: | Annals of the Rheumatic Diseases, 73(5), 890-896. BMJ Publishing Group |
| ISSN: | 1468-2060 0003-4967 |
| DOI: | 10.1136/annrheumdis-2012-202803 |
| Popis: | Objectives To investigate the contribution of genetic polymorphisms of toll like receptor (TLR) 9 and related genes on the susceptibility and clinical manifestation of anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides (AAV). Methods Four single nucleotide polymorphisms (SNPs) in TLR9 were genotyped in 863 German AAV cases and 1344 healthy controls. Significant results were replicated in a cohort of 426 Dutch and British AAV cases. 11 polymorphisms in TLR9 related genes were studied concomitantly. Results A strong association of TLR9 genotypes and haplotypes with granulomatosis with polyangiitis was observed as well as a contrariwise association with microscopic polyangiitis. The association was confirmed when cases were compared according to ANCA status rather than to clinical entity. This was partly replicated in the second cohort leading to a striking overall difference in TLR9 allele/haplotype frequencies between proteinase 3 (PR3) ANCA+ and myeloperoxidase (MPO) ANCA+ cases (p=0.00000398, pc=0.000016, OR 1.68 (95% CI 1.35 to 2.1) for rs352140; p=0.000011, pc=0.000044, OR 1.64 (95% CI 1.31 to 2.04) for a 3-SNP haplotype). No significant association or epistatic effect was detected for TLR9 related genes: interleukin 6, interleukin 23 receptor, myeloid differentiation primary response 88, TNF receptor-associated factor 6, interleukin-1 receptor-associated kinase 4, discs large homolog 5 and nucleotide-binding oligomerisation domain containing 2. Conclusions We provide further evidence that PR3-ANCA+ AAV differs genetically from MPO-ANCA+ AAV. TLR9 signalling may be involved in disease pathology, favouring models of infectious agents triggering AAV development. |
| Databáze: | OpenAIRE |
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