Bossini-Castillo, LaraSimeon, Carmen PBeretta, LorenzoBroen, Jasper CVonk, Madelon CRíos-Fernández, RaquelEspinosa, GerardCarreira, PatriciaCamps, María TCastillo, Maria JGonzález-Gay, Miguel ABeltrán, EmmaCarmen Freire, María delNarváez, JavierTolosa, CarlosWitte, TorstenKreuter, AlexanderSchuerwegh, Annemie JHoffmann-Vold, Anna-MariaHesselstrand, RogerLunardi, Claudiovan Laar, Jacob MChee, Meng MayHerrick, ArianeKoeleman, Bobby PcDenton, Christopher PFonseca, CarmenRadstake, Timothy RdjMartin, Javier2013-10-022013-10-022012-04-24Bossini-Castillo L, Simeon CP, Beretta L, Broen JC, Vonk MC, Ríos-Fernández R, et al. A multicenter study confirms CD226 gene association with systemic sclerosis-related pulmonary fibrosis. Arthritis Res. Ther.2012; 14(2):R851478-6354http://hdl.handle.net/10668/1308Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't;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.enAntígenos de diferenciación de linfocitos TEstudios de cohortesEstudios de asociación genéticaGenotipoFibrosis pulmonarEsclerodermia sistémicaMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort StudiesMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Genetic Association StudiesMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic VariationMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::GenotypeMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single NucleotideMedical Subject Headings::Diseases::Respiratory Tract Diseases::Lung Diseases::Pulmonary FibrosisMedical Subject Headings::Diseases::Skin and Connective Tissue Diseases::Connective Tissue Diseases::Scleroderma, SystemicMedical Subject Headings::Chemicals and Drugs::Biological Factors::Biological Markers::Antigens, Differentiation::Antigens, Differentiation, T-Lymphocyteresearch article22531499open access10.1186/ar38091478-6362PMC3446459