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A multicentre study confirms CD226 gene association with Systemic Sclerosis-related pulmonary fibrosis

AuthorsBossini-Castillo, L.; Simeón, Carmen P.; Beretta, L.; Broen, Jasper C.; Vonk, Madelon C.; Ríos-Fernández, Raquel; Espinosa, G.; Carreira, P.; Camps, M. T.; Castillo, María J.; González-Gay, M. A.; Beltrán, E.; Freire, María del Carmen; Narváez, J.; Tolosa, Carlos; Witte, T.; Kreuter, A.; Schuerwegh, A. J.; Hoffmann-Vold, A. M.; Hesselstrand, R.; Lunardi, C.; Laar, Jacob M. van; Chee, M. M.; Herrick, A.; Koeleman, B. P.; Denton, C.; Fonseca, C.; Radstake, T. R.; Martín, J.; Scleroderma Group, Spanish
Issue Date24-Apr-2012
PublisherBioMed Central
CitationArthritis Research & Therapy 14(2) : R85 (2012)
AbstractAbstract 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.
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