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

Lookup NU author(s): Professor Jaap Van Laar



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.

Publication metadata

Author(s): Bossini-Castillo L, Simeon CP, Beretta L, Broen JC, Vonk MC, Rios-Fernandez R, Espinosa G, Carreira P, Camps MT, Castillo MJ, Gonzalez-Gay MA, Beltran E, Freire MD, Narvaez J, Tolosa C, Witte T, Kreuter A, Schuerwegh AJ, Hoffmann-Vold AM, Hesselstrand R, Lunardi C, van Laar JM, Chee MM, Herrick A, Koeleman BPC, Denton CP, Fonseca C, Radstake TRDJ, Martin J, Spanish Scleroderma Grp

Publication type: Article

Publication status: Published

Journal: Arthritis Research & Therapy

Year: 2012

Volume: 14

Issue: 2

Print publication date: 24/04/2012

Date deposited: 04/01/2013

ISSN (electronic): 1478-6354

Publisher: BioMed Central Ltd.


DOI: 10.1186/ar3809


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Funder referenceFunder name
Fondo Europeo de Desarrollo Regional (FEDER)
VIDI laureate from the Dutch Association of Research (NWO)
Dutch Arthritis Foundation (National Reumafonds)
GENFER from the Spanish Society of Rheumatology
Orphan Disease Program grant from the European League Against Rheumatism (EULAR)
Redes Tematicas de Investigacion Cooperativa Sanitaria Program
2008.40.001Dutch Diabetes Research Foundation
1031/6.1DFG WI
CTS-4977Junta de Andalucia, Spain
PI-0590-2010Consejeria de Salud, Junta de Andalucia, Spain
NR 09-1-408Dutch Arthritis Foundation (Reumafonds)
RD08/0075Instituto de Salud Carlos III (ISCIII), Spain
SAF2009-11110Spanish Ministry of Science