OBJECTIVE: The nonsynonymous polymorphism rs763361 of the CD226 gene, which encodes DNAX accessory molecule 1, which is involved in T cell costimulation pathways, has recently been identified as a genetic risk factor for autoimmunity. The purpose of this study was to test for association of the CD226 rs763361 polymorphism with systemic sclerosis (SSc) in European Caucasian populations. METHODS: CD226 rs763361 was genotyped in 3,632 individuals, consisting of a discovery sample (991 SSc patients and 1,008 controls) and a replication sample (999 SSc patients and 634 controls). All study subjects were of European Caucasian origin. Expression of CD226 was assessed on peripheral blood mononuclear cells obtained from 21 healthy donors genotyped for CD226 rs763361. RESULTS: The CD226 rs763361 T allele was found to be associated with SSc in both the discovery and the replication samples, showing the following results in the combined populations: odds ratio (OR) 1.22 (95% confidence interval [95% CI] 1.10-1.34), P = 5.69 × 10(-5) . The CD226 T allele was also associated with various SSc subsets, highlighting a potential contribution to disease severity. The most remarkable associations of the CD226 TT risk genotype were observed with the diffuse cutaneous SSc subtype, the anti-topoisomerase I antibody-positive, and SSc-related fibrosing alveolitis subsets: OR 1.86 (95% CI 1.42-2.43), P = 5.15 × 10(-6) , OR 1.82 (95% CI 1.38-2.40), P = 2.16 × 10(-5) , and OR 1.61 (95% CI 1.25-2.08), P = 2.73 × 10(-4) , respectively. CD226 expression was not significantly influenced by CD226 rs763361 genotypes whatever the T cell subtype investigated. CONCLUSION: Our results establish CD226 as a new SSc genetic susceptibility factor underlying the contribution of costimulation pathways in the pathogenesis of SSc. Further work is nevertheless needed to define the causal variant at the CD226 locus as well as the functional consequences.
OBJECTIVE: The nonsynonymous polymorphism rs763361 of the CD226 gene, which encodes DNAX accessory molecule 1, which is involved in T cell costimulation pathways, has recently been identified as a genetic risk factor for autoimmunity. The purpose of this study was to test for association of the CD226rs763361 polymorphism with systemic sclerosis (SSc) in European Caucasian populations. METHODS:CD226rs763361 was genotyped in 3,632 individuals, consisting of a discovery sample (991 SSc patients and 1,008 controls) and a replication sample (999 SSc patients and 634 controls). All study subjects were of European Caucasian origin. Expression of CD226 was assessed on peripheral blood mononuclear cells obtained from 21 healthy donors genotyped for CD226rs763361. RESULTS: The CD226rs763361 T allele was found to be associated with SSc in both the discovery and the replication samples, showing the following results in the combined populations: odds ratio (OR) 1.22 (95% confidence interval [95% CI] 1.10-1.34), P = 5.69 × 10(-5) . The CD226 T allele was also associated with various SSc subsets, highlighting a potential contribution to disease severity. The most remarkable associations of the CD226 TT risk genotype were observed with the diffuse cutaneous SSc subtype, the anti-topoisomerase I antibody-positive, and SSc-related fibrosing alveolitis subsets: OR 1.86 (95% CI 1.42-2.43), P = 5.15 × 10(-6) , OR 1.82 (95% CI 1.38-2.40), P = 2.16 × 10(-5) , and OR 1.61 (95% CI 1.25-2.08), P = 2.73 × 10(-4) , respectively. CD226 expression was not significantly influenced by CD226rs763361 genotypes whatever the T cell subtype investigated. CONCLUSION: Our results establish CD226 as a new SSc genetic susceptibility factor underlying the contribution of costimulation pathways in the pathogenesis of SSc. Further work is nevertheless needed to define the causal variant at the CD226 locus as well as the functional consequences.
Authors: Debendra Pattanaik; Monica Brown; Bradley C Postlethwaite; Arnold E Postlethwaite Journal: Front Immunol Date: 2015-06-08 Impact factor: 7.561
Authors: Lara Bossini-Castillo; Carmen P Simeon; Lorenzo Beretta; Jasper C Broen; Madelon C Vonk; Raquel Ríos-Fernández; Gerard Espinosa; Patricia Carreira; María T Camps; Maria J Castillo; Miguel A González-Gay; Emma Beltrán; María del Carmen Freire; Javier Narváez; Carlos Tolosa; Torsten Witte; Alexander Kreuter; Annemie J Schuerwegh; Anna-Maria Hoffmann-Vold; Roger Hesselstrand; Claudio Lunardi; Jacob M van Laar; Meng May Chee; Ariane Herrick; Bobby Pc Koeleman; Christopher P Denton; Carmen Fonseca; Timothy Rdj Radstake; Javier Martin Journal: Arthritis Res Ther Date: 2012-04-24 Impact factor: 5.156
Authors: Lara Bossini-Castillo; Carmen P Simeon; Lorenzo Beretta; Jasper Broen; Madelon C Vonk; José Luis Callejas; Patricia Carreira; Luis Rodríguez-Rodríguez; Rosa García-Portales; Miguel A González-Gay; Ivan Castellví; María Teresa Camps; Carlos Tolosa; Esther Vicente-Rabaneda; María Victoria Egurbide; Annemie J Schuerwegh; Roger Hesselstrand; Claudio Lunardi; Jacob M van Laar; Paul Shiels; Ariane Herrick; Jane Worthington; Christopher Denton; Timothy R D J Radstake; Carmen Fonseca; Javier Martin Journal: Arthritis Res Ther Date: 2012-12-27 Impact factor: 5.156