title: A multicenter study confirms CD226 gene association with systemic sclerosis-related pulmonary fibrosis.
abstract: BACKGROUND
  CD226 genetic variants have been associated with a number of autoimmune diseases and recently with systemic sclerosis (SSc). The aim of this study was to test the influence of CD226 loci in SSc susceptibility, clinical phenotypes and autoantibody status in a large multicenter European population.
  
  
  METHODS
  A total of seven European populations of Caucasian ancestry were included, comprising 2,131 patients with SSc and 3,966 healthy controls. Three CD226 single nucleotide polymorphisms (SNPs), rs763361, rs3479968 and rs727088, were genotyped using Taqman 5'allelic discrimination assays.
  
  
  RESULTS
  Pooled analyses showed no evidence of association of the three SNPs, neither with the global disease nor with the analyzed subphenotypes. However, haplotype block analysis revealed a significant association for the TCG haplotype (SNP order: rs763361, rs34794968, rs727088) with lung fibrosis positive patients (PBonf = 3.18E-02 OR 1.27 (1.05 to 1.54)).
  
  
  CONCLUSIONS
  Our data suggest that the tested genetic variants do not individually influence SSc susceptibility but a CD226 three-variant haplotype is related with genetic predisposition to SSc-related pulmonary fibrosis.
authors.affiliation: Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, Avenida del Conocimiento s/n, Granada, 18100, Spain. larabc@ipb.csic.es
authors.forename: Lara
authors.initials: L
authors.lastname: Bossini-Castillo
authors.forename: Carmen P
authors.initials: CP
authors.lastname: Simeon
authors.forename: Lorenzo
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authors.lastname: Beretta
authors.forename: Jasper C
authors.initials: JC
authors.lastname: Broen
authors.forename: Madelon C
authors.initials: MC
authors.lastname: Vonk
authors.forename: Raquel
authors.initials: R
authors.lastname: Ríos-Fernández
authors.forename: Gerard
authors.initials: G
authors.lastname: Espinosa
authors.forename: Patricia
authors.initials: P
authors.lastname: Carreira
authors.forename: María T
authors.initials: MT
authors.lastname: Camps
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Castillo
authors.forename: Miguel A
authors.initials: MA
authors.lastname: González-Gay
authors.forename: Emma
authors.initials: E
authors.lastname: Beltrán
authors.forename: María del
authors.initials: Md
authors.lastname: Carmen Freire
authors.forename: Javier
authors.initials: J
authors.lastname: Narváez
authors.forename: Carlos
authors.initials: C
authors.lastname: Tolosa
authors.forename: Torsten
authors.initials: T
authors.lastname: Witte
authors.forename: Alexander
authors.initials: A
authors.lastname: Kreuter
authors.forename: Annemie J
authors.initials: AJ
authors.lastname: Schuerwegh
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Hoffmann-Vold
authors.forename: Roger
authors.initials: R
authors.lastname: Hesselstrand
authors.forename: Claudio
authors.initials: C
authors.lastname: Lunardi
authors.forename: Jacob M
authors.initials: JM
authors.lastname: van Laar
authors.forename: Meng May
authors.initials: MM
authors.lastname: Chee
authors.forename: Ariane
authors.initials: A
authors.lastname: Herrick
authors.forename: Bobby Pc
authors.initials: BP
authors.lastname: Koeleman
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Denton
authors.forename: Carmen
authors.initials: C
authors.lastname: Fonseca
authors.forename: Timothy Rdj
authors.initials: TR
authors.lastname: Radstake
authors.forename: Javier
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authors.lastname: Martin
mesh_terms: D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011658:Pulmonary Fibrosis / Q000453:epidemiology / Q000235:genetics*; D012595:Scleroderma, Systemic / Q000453:epidemiology / Q000235:genetics*; D000098862:T Lineage-Specific Activation Antigen 1
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1