@article{10902/31323,
year = {2012},
month = {4},
url = {https://hdl.handle.net/10902/31323},
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 (PBonf = 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.},
organization = {We thank Sofia Vargas, Sonia García and Gema Robledo for their excellent technical assistance and all the patients and control donors for their essential collaboration. We thank Banco Nacional de ADN (University of Salamanca, Spain) and the Norwegian Bone Marrow Donor Registry, who supplied part of the control DNA samples. We are also thankful to EUSTAR (the EULAR Scleroderma Trials and Research group) and the German Network of Systemic Sclerosis for the facilitation of this project.

This work was supported by the following grants: JM was funded by GEN-FER from the Spanish Society of Rheumatology, SAF2009-11110 from the Spanish Ministry of Science, CTS-4977 from Junta de Andalucía, Spain, in part by Redes Temáticas de Investigación Cooperativa Sanitaria Program, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII), Spain and by Fondo Europeo de Desarrollo Regional (FEDER). TRDJR was funded by the VIDI laureate from the Dutch Association of Research (NWO) and Dutch Arthritis Foundation (National Reumafonds). JM and TRDJR were sponsored by the Orphan Disease Program grant from the European League Against Rheumatism (EULAR). BPCK is supported by the Dutch Diabetes Research Foundation (grant 2008.40.001) and the Dutch Arthritis Foundation (Reumafonds, grant NR 09-1-408). TW was granted by DFG WI 1031/6.1. This study was also funded by PI-0590-2010, Consejería de Salud, Junta de Andalucía, Spain.

The Spanish Scleroderma Group: Norberto Ortego-Centeno and Jose Luis Callejas, Unidad de Enfermedades Sistémicas Autoinmunes, Servicio de Medicina Interna, Hospital Clínico Universitario San Cecilio, Granada; Nuria Navarrete, Servicio de Medicina Interna, Hospital Virgen de las Nieves, Granada; Rosa García Portales, Servicio de Reumatología, Hospital Virgen de la Victoria, Málaga; Antonio Fernández-Nebro, Servicio de Reumatología, Hospital Carlos Haya, Málaga; María F. González-Escribano, Servicio de Inmunología, Hospital Virgen del Rocío, Sevilla; Julio Sánchez-Román and Francisco José García-Hernández, Servicio de Medicina Interna, Hospital Virgen del Rocío, Sevilla; Mª Ángeles Aguirre and Inmaculada Gómez-Gracia, Servicio de Reumatología, Hospital Reina Sofía, Córdoba; Benjamín Fernández-Gutiérrez and Luis Rodríguez-Rodríguez, Servicio de Reumatología, Hospital Clínico San Carlos, Madrid; José Luis Andreu and Mónica Fernández de Castro, Servicio de Reumatología, Hospital Puerta del Hierro, Madrid; Paloma García de la Peña, Servicio de Reumatología, Hospital Madrid Norte Sanchinarro, Madrid; Francisco Javier López-Longo and Lina Martínez, Servicio de Reumatología, Hospital General Universitario Gregorio Marañón, Madrid; Vicente Fonollosa, Servicio de Medicina Interna, Hospital Valle de Hebrón, Barcelona; Iván Castellví, Servicio de Reumatología, Hospital Sant Pau, Barcelona; Anna Pros, Servicio de Reumatología, Hospital Del Mar, Barcelona; Mónica Rodríguez Carballeira, Servicio de Medicina Interna, Hospital Universitari Mútua Terrasa, Barcelona; Bernardino Díaz, Luis Trapiella and María Gallego, Servicio de Medicina Interna, Hospital Central de Asturias, Oviedo; Inés Vaqueiro, Unidad de Trombosis y Vasculitis, Servicio de Medicina Interna, Hospital Xeral-Complexo Hospitalario Universitario de Vigo, Vigo; María Victoria Egurbide, Servicio de Medicina Interna, Hospital de Cruces, Barakaldo; Luis Sáez-Comet, Unidad de Enfermedades Autoinmunes Sistémicas, Servicio de Medicina Interna, Hospital Universitario Miguel Servet, Zaragoza; Federico Díaz and Vanesa Hernández, Servicio de Reumatología, Hospital Universitario de Canarias, Tenerife; José Andrés Román-Ivorra, Servicio de Reumatología, Hospital Universitari i Politecnic La Fe, Valencia.},
publisher = {BioMed Central},
publisher = {Arthritis Research & Therapy, 2012, 14(2), R85},
title = {A multicenter study confirms CD226 gene association with systemic sclerosis-related pulmonary fibrosis},
author = {Bossini-Castillo, Lara and Simeón, Carmen P. and Beretta, Lorenzo and Broen, Jaster C. and Vonk, Madelon C. and Ríos-Fernández, Raquel and Espinosa, Gerard and Carreira, Patricia and Camps, María T. and Castillo, María J. and González-Gay Mantecón, Miguel Ángel and Beltrán, Emma and Freire, María del Carmen and Narváez, Javier and Tolosa, Carlos and Witte, Torsten and Kreuter, Alexander and Schuerwegh, Annemie, J. and Hoffman-Vold, Anna-Maria and Hesselstrand, Roger},
}