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Implication of IL-2/IL-21 region in systemic sclerosis genetic susceptibility

2012; BMJ; Volume: 72; Issue: 7 Linguagem: Inglês

10.1136/annrheumdis-2012-202357

1468-2060

Lina‐Marcela Diaz‐Gallo, Carmen Pilar Simeón‐Aznar, Jasper Broen, Norberto Ortego‐Centeno, Lorenzo Beretta, Madelon C Vonk, Patrícia Carreira, Sofía Vargas, José Andrés Román-Ivorra, Miguel Á. González‐Gay, Carlos Tolosa, Francisco Javier López-Longo, Gerard Espinosa, Esther Vicente, Roger Hesselstrand, Gabriela Riemekasten, Torsten Witte, Jörg H. W. Distler, Alexandre E. Voskuyl, Annemie J. Schuerwegh, Paul G. Shiels, Annica Nordin, Leonid Padyukov, Anna‐Maria Hoffmann‐Vold, R Scorza, Claudio Lunardi, Paolo Airò, Jacob M. van Laar, Nicolas Hunzelmann, Birgit Gathof, Alexander Kreuter, Ariane L. Herrick, Jane Worthington, Christopher P. Denton, Xiaodong Zhou, Frank C. Arnett, Carmen Fonseca, Bobby PC Koeleman, Shervin Assasi, Timothy R. D. J. Radstake, Maureen D. Mayes, Javier Martı́n,

Skin Diseases and Diabetes

Objective The interleukin 2 ( IL-2 ) and interleukin 21 ( IL-21) locus at chromosome 4q27 has been associated with several autoimmune diseases, and both genes are related to immune system functions. The aim of this study was to evaluate the role of the IL-2/IL-21 locus in systemic sclerosis (SSc). Patients and methods The case control study included 4493 SSc Caucasian patients and 5856 healthy controls from eight Caucasian populations (Spain, Germany, The Netherlands, USA, Italy, Sweden, UK and Norway). Four single nucleotide polymorphisms (rs2069762, rs6822844, rs6835457 and rs907715) were genotyped using TaqMan allelic discrimination assays. Results We observed evidence of association of the rs6822844 and rs907715 variants with global SSc (p c =6.6E-4 and p c =7.2E-3, respectively). Similar statistically significant associations were observed for the limited cutaneous form of the disease. The conditional regression analysis suggested that the most likely genetic variation responsible for the association was the rs6822844 polymorphism. Consistently, the rs2069762A-rs6822844T-rs6835457G-rs907715T allelic combination showed evidence of association with SSc and limited cutaneous SSc subtype (p c =1.7E-03 and p c =8E-4, respectively). Conclusions These results suggested that the IL-2/IL-21 locus influences the genetic susceptibility to SSc. Moreover, this study provided further support for the IL-2/IL-21 locus as a common genetic factor in autoimmune diseases.