TY - JOUR
T1 - A multicenter study confirms CD226 gene association with systemic sclerosis-related pulmonary fibrosis
AU - Bossini-Castillo, Lara
AU - Simeon, Carmen P.
AU - Beretta, Lorenzo
AU - Broen, Jasper C.
AU - Vonk, Madelon C.
AU - Ríos-Fernández, Raquel
AU - Espinosa, Gerard
AU - Carreira, Patricia
AU - Camps, María T.
AU - Castillo, Maria J.
AU - González-Gay, Miguel A.
AU - Beltrán, Emma
AU - Carmen Freire, María D.
AU - Narváez, Javier
AU - Tolosa, Carlos
AU - Witte, Torsten
AU - Kreuter, Alexander
AU - Schuerwegh, Annemie J.
AU - Hoffmann-Vold, Anna Maria
AU - Hesselstrand, Roger
AU - Lunardi, Claudio
AU - van Laar, Jacob M.
AU - Chee, Meng M.
AU - Herrick, Ariane
AU - Koeleman, Bobby P C
AU - Denton, Christopher P.
AU - Fonseca, Carmen
AU - Radstake, Timothy R D J
AU - Martin, Javier
PY - 2012/4/24
Y1 - 2012/4/24
N2 - 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. © 2012 Bossini-Castillo et al.; licensee BioMed Central Ltd.
AB - 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. © 2012 Bossini-Castillo et al.; licensee BioMed Central Ltd.
KW - Antigens, Differentiation, T-Lymphocyte
KW - Cohort Studies
KW - Female
KW - Genetic Association Studies
KW - Genetic Variation
KW - Genotype
KW - Humans
KW - Male
KW - Polymorphism, Single Nucleotide
KW - Pulmonary Fibrosis
KW - Scleroderma, Systemic
KW - Journal Article
KW - Multicenter Study
KW - Research Support, Non-U.S. Gov't
UR - http://www.scopus.com/inward/record.url?scp=84859935899&partnerID=8YFLogxK
U2 - 10.1186/ar3809
DO - 10.1186/ar3809
M3 - Article
C2 - 22531499
SN - 1478-6354
VL - 14
SP - R85
JO - Arthritis research & therapy
JF - Arthritis research & therapy
IS - 2
M1 - R85
ER -