title: A candidate gene study identifies a haplotype of CD2 as novel susceptibility factor for systemic sclerosis.
abstract: OBJECTIVE
  Systemic sclerosis (SSc) is a rare autoimmune disease (AID) with a complex genetic etiology. Evidence for a shared pathogenesis across AIDs is given by the well-known pleiotropism of autoimmune genes. Recently, several unbiased approaches have identified an association between polymorphisms of the CD2 gene, and rheumatoid arthritis (RA) susceptibility. The objective of this study was to investigate whether CD2 polymorphisms are associated with SSc.
  
  
  METHODS
  Two SNPs of CD2, rs624988 and rs798036, were genotyped in a total of 1,786 SSc patients and 2,360 healthy individuals from two European populations (France and Italy). Meta-analyses were performed to assess whether an association exists between CD2 polymorphisms or haplotypes and SSc or its main subtypes.
  
  
  RESULTS
  The combined analyses revealed an association between the rs624988 A allele and SSc susceptibility: padj=0.023, OR=1.14 (95%CI 1.04-1.25). Single marker analysis did not reveal any association between rs798036 and SSc. Haplotype analysis identified that the A-T haplotype, previously described in RA, was associated with higher susceptibility for SSc (padj=0.029, OR=1.14, 95%CI 1.04-1.25) and with the positive anti-centromere antibody sub-group of SSc patients (padj=0.009, OR=1.19 95%CI 1.07-1.32). Genotype-mRNA expression correlations revealed that the CD2 risk haplotype was associated with decreased CD2 mRNA expression in SSc patients.
  
  
  CONCLUSIONS
  Our study establishes CD2 as a new susceptibility factor for SSc, in a European Caucasian population, confirming the sharing of autoimmune risk factors by SSc and RA.
authors.affiliation: INSERM, Institut Cochin, INSERM U1016, Sorbonne Paris Cité, and Paris Descartes University, Paris; and Paris Descartes University, Rheumatology A Department, Cochin Hospital, APHP, Paris, France.
authors.forename: Eugenie
authors.initials: E
authors.lastname: Koumakis
authors.affiliation: UMR CNRS-8071/INRA-1152, Université d'Evry Val d'Essonne, Evry, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Bouaziz
authors.affiliation: Paris Diderot University, Rheumatology Department, Hôpital Bichat Claude Bernard, APHP, Paris; and Paris Diderot University, INSERM U699, Hôpital Bichat Claude Bernard, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Dieudé
authors.affiliation: INSERM, Institut Cochin, INSERM U1016, Sorbonne Paris Cité, and Paris Descartes University, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Cauvet
authors.affiliation: INSERM, Institut Cochin, INSERM U1016, Sorbonne Paris Cité, and Paris Descartes University, Paris, France.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ruiz
authors.affiliation: Rheumatology and Clinical Immunology, Spedali Civili, Brescia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Airò
authors.affiliation: Institute of Biomedical Technologies, National Centre of Research, Milan, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Cusi
authors.affiliation: Department of Experimental and Clinical Medicine, Division of Rheumatology, AOUC, University of Florence, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Matucci-Cerinic
authors.affiliation: Department of Health Sciences, University of Milan, Italy.
authors.forename: Erika
authors.initials: E
authors.lastname: Salvi
authors.affiliation: Department of Clinical and Experimental Medicine, Rheumatology Unit, Second University of Naples, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cuomo
authors.affiliation: Department of Internal Medicine, Hôpital Claude Huriez, Université de Lille II, Lille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Hachulla
authors.affiliation: INSERM U618, IFR 135, CHU Bretonneau, Tours, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Diot
authors.affiliation: Unità di Reumatologia, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Caramaschi
authors.affiliation: Rheumatology, Department of Internal Medicine and Medical Specialities, "Sapienza" University of Rome, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Riccieri
authors.affiliation: INSERM, Institut Cochin, INSERM U1016, Sorbonne Paris Cité, and Paris Descartes University, Paris; and Paris Descartes University, Rheumatology A Department, Cochin Hospital, APHP, Paris, France.
authors.forename: Jerome
authors.initials: J
authors.lastname: Avouac
authors.affiliation: INSERM, Institut Cochin, INSERM U1016, Sorbonne Paris Cité, and Paris Descartes University, Paris; and Paris Descartes University, Rheumatology A Department, Cochin Hospital, APHP, Paris, France. yannick.allanore@cch.aphp.fr.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Allanore
mesh_terms: D000328:Adult; D000368:Aged; D015551:Autoimmunity / Q000235:genetics*; D018801:CD2 Antigens / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D005602:France / Q000453:epidemiology; D005787:Gene Frequency; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012595:Scleroderma, Systemic / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D044465:White People / Q000235:genetics
chemical_list: D018801:CD2 Antigens; D005819:Genetic Markers