title: Association study of ITGAM, ITGAX, and CD58 autoimmune risk loci in systemic sclerosis: results from 2 large European Caucasian cohorts.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Université Paris Descartes, Rhumatologie A, Hôpital Cochin, APHP, Paris, France.
authors.forename: Baptiste
authors.initials: B
authors.lastname: Coustet
authors.forename: Sandeep K
authors.initials: SK
authors.lastname: Agarwal
authors.forename: Pravitt
authors.initials: P
authors.lastname: Gourh
authors.forename: Mickael
authors.initials: M
authors.lastname: Guedj
authors.forename: Maureen D
authors.initials: MD
authors.lastname: Mayes
authors.forename: Philippe
authors.initials: P
authors.lastname: Dieude
authors.forename: Julien
authors.initials: J
authors.lastname: Wipff
authors.forename: Jerome
authors.initials: J
authors.lastname: Avouac
authors.forename: Eric
authors.initials: E
authors.lastname: Hachulla
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Diot
authors.forename: Jean Luc
authors.initials: JL
authors.lastname: Cracowski
authors.forename: Kiet
authors.initials: K
authors.lastname: Tiev
authors.forename: Jean
authors.initials: J
authors.lastname: Sibilia
authors.forename: Luc
authors.initials: L
authors.lastname: Mouthon
authors.forename: Camille
authors.initials: C
authors.lastname: Frances
authors.forename: Zahir
authors.initials: Z
authors.lastname: Amoura
authors.forename: Patrick
authors.initials: P
authors.lastname: Carpentier
authors.forename: Olivier
authors.initials: O
authors.lastname: Meyer
authors.forename: Andre
authors.initials: A
authors.lastname: Kahan
authors.forename: Catherine
authors.initials: C
authors.lastname: Boileau
authors.forename: Frank C
authors.initials: FC
authors.lastname: Arnett
authors.forename: Yannick
authors.initials: Y
authors.lastname: Allanore
mesh_terms: D001327:Autoimmune Diseases / Q000235:genetics*; D039481:CD11b Antigen / Q000235:genetics*; D039521:CD11c Antigen / Q000235:genetics*; D018968:CD58 Antigens / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D003627:Data Interpretation, Statistical; D005260:Female; D005602:France; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D012595:Scleroderma, Systemic / Q000235:genetics*; D014481:United States; D044465:White People / Q000235:genetics*
chemical_list: D039481:CD11b Antigen; D039521:CD11c Antigen; D018968:CD58 Antigens; C509295:ITGAM protein, human