Abstract
Objective. Accumulating evidence shows that shared autoimmunity is critical for the pathogenesis of many autoimmune diseases. Systemic sclerosis (SSc) belongs to the connective tissue disorders, and recent data have highlighted strong associations with autoimmunity genes shared with other autoimmune diseases. To determine whether novel risk loci associated with systemic lupus erythematosus or multiple sclerosis may confer susceptibility to SSc, we tested single-nucleotide polymorphisms (SNP) from ITGAM, ITGAX, and CD58 for associations.
Methods. SNP harboring associations with autoimmune diseases, ITGAM rs9937837, ITGAX rs11574637, and CD58 rs12044852, were genotyped in 2 independent cohorts of European Caucasian ancestry: 1031 SSc patients and 1014 controls from France and 1038 SSc patients and 691 controls from the USA, providing a combined study population of 3774 individuals. ITGAM rs1143679 was additionally genotyped in the French cohort.
Results. The 4 polymorphisms were in Hardy-Weinberg equilibrium in the 2 control populations, and allelic frequencies were similar to those expected in European Caucasian populations. Allelic and genotypic frequencies for these 3 SNP were found to be statistically similar in SSc patients and controls. Subphenotype analyses for subgroups having diffuse cutaneous subtype disease, specific autoantibodies, or fibrosing alveolitis did not reveal any difference between SSc patients and controls.
Conclusion. These results obtained through 2 large cohorts of SSc patients of European Caucasian ancestry do not support the implication of ITGAM, ITGAX, and CD58 genes in the genetic susceptibility of SSc, although they were recently identified as autoimmune disease risk genes.
- SYSTEMIC SCLEROSIS
- SYSTEMIC LUPUS ERYTHEMATOSUS
- AUTOIMMUNITY
- SINGLE NUCLEOTIDE POLYMORPHISM
- ITGAM
- ITGAX
- CD58
Footnotes
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Supported by Association des Sclérodermiques de France, INSERM; and by Groupe Français de Recherche sur la Sclérodermie and Agence Nationale pour la Recherche (grant no. R07094KS). The US studies were supported by NIH/NIAMS Scleroderma Family Registry and DNA Repository (N01-AR-0-2251) and NIH/NIAMS Center of Research Translation in Scleroderma (1P50AR054144).
- Accepted for publication January 13, 2011.