Implication of IL-2/IL-21 region in systemic sclerosis genetic susceptibility. Issue 7 (21st November 2012)

• Record Type: Journal Article
• Authors: Diaz-Gallo, Lina-Marcela; Simeon, Carmen P; Broen, Jasper C; Ortego-Centeno, Norberto; Beretta, Lorenzo; Vonk, Madelon C; Carreira, Patricia E; Vargas, Sofia; Román-Ivorra, José Andrés; González-Gay, Miguel A; Tolosa, Carlos; López-Longo, Francisco Javier; Espinosa, Gerard; Vicente, Esther F; Hesselstrand, Roger; Riemekasten, Gabriela; Witte, Torsten; Distler, Jörg H W; Voskuyl, Alexandre E; Schuerwegh, Annemie J; Shiels, Paul G; Nordin, Annika; Padyukov, Leonid; Hoffmann-Vold, Anna-Maria; Scorza, Raffaella; Lunardi, Claudio; Airo, Paolo; van Laar, Jacob M; Hunzelmann, Nicolas; Gathof, Birgit S; Kreuter, Alexander; Herrick, Ariane; Worthington, Jane; Denton, Christopher P; Zhou, Xiaodong; Arnett, Frank C; Fonseca, Carmen; Koeleman, Bobby PC; Assasi, Shervin; Radstake, Timothy R D J; Mayes, Maureen D; Martín, Javier;
• Other Names: Callejas Jose Luis author non-byline.; Ríos Raquel author non-byline.; Navarrete Nuria author non-byline.; Portales Rosa García author non-byline.; Camps María Teresa author non-byline.; Fernández-Nebro Antonio author non-byline.; González-Escribano María F. author non-byline.; Sánchez-Román Julio author non-byline.; García-Hernández Francisco J author non-byline.; Castillo Mª Jesús author non-byline.; Aguirre Mª Ángeles author non-byline.; Gómez-Gracia Inmaculada author non-byline.; Fernández-Gutiérrez Benjamín author non-byline.; Rodríguez-Rodríguez Luis author non-byline.; Andreu José Luis author non-byline.; de la Peña Paloma García author non-byline.; Martínez Lina author non-byline.; Robles María Ángeles author non-byline.; Oreiro Natividad author non-byline.; de Reumatología Servicio author non-byline.; Fonollosa Vicente author non-byline.; Pros Anna author non-byline.; Carballeira Mónica Rodríguez author non-byline.; Narváez Francisco Javier author non-byline.; Díaz Bernardino author non-byline.; Trapiella Luis author non-byline.; Gallego María author non-byline.; del Carmen Freire María author non-byline.; Vaqueiro Inés author non-byline.; Egurbide María Victoria author non-byline.; Sáez-Comet Luis author non-byline.; Díaz Federico author non-byline.; Hernández Vanesa author non-byline.; Beltrán Emma author non-byline.;
• Is Part Of: Annals of the rheumatic diseases. Volume 72:Issue 7(2013)
• Page Start: 1233
• Page End: 1238
• Publication Date: 2012-11-21
• Subjects: Systemic Sclerosis -- Gene Polymorphism -- Autoimmune Diseases; Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2012-202357
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : 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 (pc =6.6E-4 and pc =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 (pc =1.7E-03 and pc =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.