A multicenter study confirms CD226 gene association with systemic sclerosis-related pulmonary fibrosis

Lara Bossini-Castillo, Carmen P. Simeon, Lorenzo Beretta, Jasper C. Broen, Madelon C. Vonk, Raquel Ríos-Fernández, Gerard Espinosa, Patricia Carreira, María T. Camps, Maria J. Castillo, Miguel A. González-Gay, Emma Beltrán, María D. Carmen Freire, Javier Narváez, Carlos Tolosa, Torsten Witte, Alexander Kreuter, Annemie J. Schuerwegh, Anna Maria Hoffmann-Vold, Roger HesselstrandClaudio Lunardi, Jacob M. van Laar, Meng M. Chee, Ariane Herrick, Bobby P C Koeleman, Christopher P. Denton, Carmen Fonseca, Timothy R D J Radstake, Javier Martin

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: 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 (P Bonf = 3.18E-02 OR 1.27 (1.05 to 1.54)).Conclusion: 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.

Original languageEnglish
Article numberR85
JournalArthritis Research and Therapy
Volume14
Issue number2
DOIs
Publication statusPublished - Apr 24 2012

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Immunology and Allergy
  • Medicine(all)

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