CT60 and +49 polymorphisms of CTLA 4 are associated with ANCA-positive small vessel vasculitis
Objective. To investigate whether single nucleotide polymorphisms (SNPs) within cytotoxic T-lymphocyte antigen-4 (CTLA-4) are associated with ANCA-associated small vessel vasculitis (SVV). Methods. The CTLA-4 CT60 (exon 4), +49 (exon 1) and −318 (promoter region) genotypes were determined by PCR and...
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| Published in | Rheumatology (Oxford, England) Vol. 48; no. 12; pp. 1502 - 1505 |
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| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Oxford
Oxford University Press
01.12.2009
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| Abstract | Objective. To investigate whether single nucleotide polymorphisms (SNPs) within cytotoxic T-lymphocyte antigen-4 (CTLA-4) are associated with ANCA-associated small vessel vasculitis (SVV). Methods. The CTLA-4 CT60 (exon 4), +49 (exon 1) and −318 (promoter region) genotypes were determined by PCR and restriction fragment length polymorphism (RFLP) in 222 white Caucasians of UK origin with SVV and 670 ethnically matched controls. Results. The CTLA-4 exon 1 (+49) and 4 (CT60) polymorphisms are associated with SVV (+49: χ2 = 10.965, P = 0.004; CT60: χ2 = 12.017, P = 0.002). Both disease-susceptible and disease-protective haplotypes have been identified in this cohort, and their frequencies are similar in the subtypes of WG and microscopic polyangiitis. Conclusion. This study provides further evidence that CTLA-4, a susceptibility locus for a number of common autoimmune diseases, may also be involved in the development of ANCA-associated SVV. |
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| AbstractList | To investigate whether single nucleotide polymorphisms (SNPs) within cytotoxic T-lymphocyte antigen-4 (CTLA-4) are associated with ANCA-associated small vessel vasculitis (SVV).
The CTLA-4 CT60 (exon 4), +49 (exon 1) and -318 (promoter region) genotypes were determined by PCR and restriction fragment length polymorphism (RFLP) in 222 white Caucasians of UK origin with SVV and 670 ethnically matched controls.
The CTLA-4 exon 1 (+49) and 4 (CT60) polymorphisms are associated with SVV (+49: chi(2) = 10.965, P = 0.004; CT60: chi(2) = 12.017, P = 0.002). Both disease-susceptible and disease-protective haplotypes have been identified in this cohort, and their frequencies are similar in the subtypes of WG and microscopic polyangiitis.
This study provides further evidence that CTLA-4, a susceptibility locus for a number of common autoimmune diseases, may also be involved in the development of ANCA-associated SVV. Objective. To investigate whether single nucleotide polymorphisms (SNPs) within cytotoxic T-lymphocyte antigen-4 (CTLA-4) are associated with ANCA-associated small vessel vasculitis (SVV). Methods. The CTLA-4 CT60 (exon 4), +49 (exon 1) and −318 (promoter region) genotypes were determined by PCR and restriction fragment length polymorphism (RFLP) in 222 white Caucasians of UK origin with SVV and 670 ethnically matched controls. Results. The CTLA-4 exon 1 (+49) and 4 (CT60) polymorphisms are associated with SVV (+49: χ2 = 10.965, P = 0.004; CT60: χ2 = 12.017, P = 0.002). Both disease-susceptible and disease-protective haplotypes have been identified in this cohort, and their frequencies are similar in the subtypes of WG and microscopic polyangiitis. Conclusion. This study provides further evidence that CTLA-4, a susceptibility locus for a number of common autoimmune diseases, may also be involved in the development of ANCA-associated SVV. To investigate whether single nucleotide polymorphisms (SNPs) within cytotoxic T-lymphocyte antigen-4 (CTLA-4) are associated with ANCA-associated small vessel vasculitis (SVV).OBJECTIVETo investigate whether single nucleotide polymorphisms (SNPs) within cytotoxic T-lymphocyte antigen-4 (CTLA-4) are associated with ANCA-associated small vessel vasculitis (SVV).The CTLA-4 CT60 (exon 4), +49 (exon 1) and -318 (promoter region) genotypes were determined by PCR and restriction fragment length polymorphism (RFLP) in 222 white Caucasians of UK origin with SVV and 670 ethnically matched controls.METHODSThe CTLA-4 CT60 (exon 4), +49 (exon 1) and -318 (promoter region) genotypes were determined by PCR and restriction fragment length polymorphism (RFLP) in 222 white Caucasians of UK origin with SVV and 670 ethnically matched controls.The CTLA-4 exon 1 (+49) and 4 (CT60) polymorphisms are associated with SVV (+49: chi(2) = 10.965, P = 0.004; CT60: chi(2) = 12.017, P = 0.002). Both disease-susceptible and disease-protective haplotypes have been identified in this cohort, and their frequencies are similar in the subtypes of WG and microscopic polyangiitis.RESULTSThe CTLA-4 exon 1 (+49) and 4 (CT60) polymorphisms are associated with SVV (+49: chi(2) = 10.965, P = 0.004; CT60: chi(2) = 12.017, P = 0.002). Both disease-susceptible and disease-protective haplotypes have been identified in this cohort, and their frequencies are similar in the subtypes of WG and microscopic polyangiitis.This study provides further evidence that CTLA-4, a susceptibility locus for a number of common autoimmune diseases, may also be involved in the development of ANCA-associated SVV.CONCLUSIONThis study provides further evidence that CTLA-4, a susceptibility locus for a number of common autoimmune diseases, may also be involved in the development of ANCA-associated SVV. |
| Author | Chavele, Konstantia-Maria Pusey, Charles Savage, Caroline O. S. Heward, Joanne M. Kamesh, Lavanya Gough, Stephen C. L. Salama, Alan Williams, Julie M. Harper, Lorraine |
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| Cites_doi | 10.1002/art.1780370206 10.1046/j.1365-2265.1998.00542.x 10.1038/sj.gene.6363655 10.1016/j.autrev.2004.06.003 10.1126/science.270.5238.985 10.1073/pnas.0706409104 10.1111/j.1365-2249.2005.02808.x 10.1186/1471-2350-8-3 10.1016/j.jneuroim.2005.04.003 10.1038/nature01621 10.1210/jc.2007-0147 10.1007/s00251-002-0429-9 10.1126/science.1069424 10.1186/1740-2557-2-8 10.1056/NEJM199007263230407 10.1136/ard.2004.025809 10.1016/j.clim.2008.03.506 10.1136/ard.58.3.193 10.1038/nrg1944 10.1002/art.20385 10.2337/db07-1736 10.1002/eji.200526168 |
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| Keywords | Vascular disease Vasculitis Antineutrophil cytoplasmic antibody Blood vessel Rheumatology Cardiovascular disease CTLA-4 Polymorphisms Polymorphism |
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| Snippet | Objective. To investigate whether single nucleotide polymorphisms (SNPs) within cytotoxic T-lymphocyte antigen-4 (CTLA-4) are associated with ANCA-associated... To investigate whether single nucleotide polymorphisms (SNPs) within cytotoxic T-lymphocyte antigen-4 (CTLA-4) are associated with ANCA-associated small vessel... |
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| SubjectTerms | Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - genetics Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - immunology Antigens, CD - genetics Biological and medical sciences Case-Control Studies CTLA-4 CTLA-4 Antigen Diseases of the osteoarticular system Gene Frequency Genetic Predisposition to Disease Genotype Haplotypes Humans Medical sciences Polymorphism, Single Nucleotide Polymorphisms Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis Vasculitis |
| Title | CT60 and +49 polymorphisms of CTLA 4 are associated with ANCA-positive small vessel vasculitis |
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