Association Study of ITGAM, ITGAX, and CD58 Autoimmune Risk Loci in Systemic Sclerosis: Results from 2 Large European Caucasian Cohorts

作者：Coustet Baptiste; Agarwal Sandeep K; Gourh Pravitt; Guedj Mickael; Mayes Maureen D; Dieude Philippe; Wipff Julien; Avouac Jerome; Hachulla Eric; Diot Elisabeth; Cracowski Jean Luc; Tiev Kiet; Sibilia Jean; Mouthon Luc; Frances Camille; Amoura Zahir; Carpentier Patrick; Meyer Olivier; Kahan Andre; Boileau Catherine; Arnett Frank C; Allanore Yannick^*

来源：Journal of Rheumatology, 2011, 38(6): 1033-1038.

DOI：10.3899/jrheum.101053

• SYSTEMIC SCLEROSIS
• SYSTEMIC LUPUS ERYTHEMATOSUS
• AUTOIMMUNITY
• SINGLE NUCLEOTIDE POLYMORPHISM
• ITGAM
• ITGAX
• CD58

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 polyrnorphisms 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. (First Release March 1 2011; J Rheumatol 2011;38:1033-8; doi:10.3899/jrheum.101053)

• 出版日期2011-6