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Association of the C8orf13-BLK region with systemic sclerosis in North-American and European populations.
- Source :
-
Journal of autoimmunity [J Autoimmun] 2010 Mar; Vol. 34 (2), pp. 155-62. Date of Electronic Publication: 2009 Sep 30. - Publication Year :
- 2010
-
Abstract
- Objective: Genetic studies in the systemic sclerosis (SSc), an autoimmune disease that clinically manifests with dermal and internal organ fibrosis and small vessel vasculopathy, have identified multiple susceptibility genes including HLA-class II, PTPN22, IRF5, and STAT4 which have also been associated with other autoimmune diseases, such as systemic lupus erythematosus (SLE). These data suggest that there are common autoimmune disease susceptibility genes. The current report sought to determine if polymorphisms in the C8orf13-BLK region (chromosome 8p23.1-B lymphoid tyrosine kinase), which is associated with SLE, are associated also with SSc.<br />Methods: Two variants in the C8orf13-BLK region (rs13277113 & rs2736340) were tested for association with 1050 SSc cases and 694 controls of North Americans of European descent and replicated in a second series 589 SSc cases and 722 controls from Spain.<br />Results: The "T" allele at rs2736340 variant was associated with SSc in both the U.S. and Spanish case-control series (P = 6.8 x 10(-5), OR 1.27, 95% CI 1.1-1.4). The "A" allele at rs13277113 variant was associated with SSc in the U.S. series only (P = 3.6 x 10(-4), OR 1.32, 95% CI 1.1-1.6) and was significant in the combined analyses of the two series (P = 2.0 x 10(-3); OR 1.20, 95% CI 1.1-1.3). Both variants demonstrated an association with the anti-centromere antibody (P = 2.2 x 10(-6) and P = 5.5 x 10(-4), respectively) and limited SSc (P = 3.3 x 10(-5) and P = 2.9 x 10(-3), respectively) in the combined analysis. Peripheral blood gene expression profiles suggest that B-cell receptor and NFkappaB signaling are dysregulated based on the risk haplotype of these variants.<br />Conclusion: We identify and replicate the association of the C8orf13-BLK region as a novel susceptibility factor for SSc, placing it in the category of common autoimmune disease susceptibility genes.<br /> (Copyright 2009 Elsevier Ltd. All rights reserved.)
- Subjects :
- Autoantibodies blood
Autoantibodies immunology
Case-Control Studies
Chromosomes, Human, Pair 8
Female
Gene Expression Profiling
Genetic Association Studies
Genotype
Humans
Lupus Erythematosus, Systemic genetics
Lupus Erythematosus, Systemic immunology
Lupus Erythematosus, Systemic physiopathology
Male
NF-kappa B genetics
NF-kappa B metabolism
Receptors, Antigen, B-Cell genetics
Receptors, Antigen, B-Cell metabolism
Scleroderma, Systemic blood
Scleroderma, Systemic immunology
Scleroderma, Systemic physiopathology
Signal Transduction genetics
Signal Transduction immunology
Spain
United States
White People
src-Family Kinases immunology
Centromere immunology
Genetic Predisposition to Disease
Polymorphism, Single Nucleotide
Scleroderma, Systemic genetics
src-Family Kinases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1095-9157
- Volume :
- 34
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of autoimmunity
- Publication Type :
- Academic Journal
- Accession number :
- 19796918
- Full Text :
- https://doi.org/10.1016/j.jaut.2009.08.014