Influence of the IL6 gene in susceptibility to systemic sclerosis

• Published in: Journal of rheumatology Vol. 39; no. 12; p. 2294
• Main Authors: Cénit, Maria Carmen, Simeón, Carmen P, Vonk, Madelon C, Callejas-Rubio, Jose L, Espinosa, Gerard, Carreira, Patricia, Blanco, Francisco J, Narvaez, Javier, Tolosa, Carlos, Román-Ivorra, José A, Gómez-García, Inmaculada, García-Hernández, Francisco J, Gallego, María, García-Portales, Rosa, Egurbide, María Victoria, Fonollosa, Vicente, García de la Peña, Paloma, López-Longo, Francisco J, González-Gay, Miguel A, Hesselstrand, Roger, Riemekasten, Gabriela, Witte, Torsten, Voskuyl, Alexandre E, Schuerwegh, Annemie J, Madhok, Rajan, Fonseca, Carmen, Denton, Christopher, Nordin, Annika, Palm, Øyvind, van Laar, Jacob M, Hunzelmann, Nicolas, Distler, Jörg H W, Kreuter, Alexander, Herrick, Ariane, Worthington, Jane, Koeleman, Bobby P, Radstake, Timothy R D J, Martín, Javier
• Format: Journal Article
• Language: English
• Published: Canada 01.12.2012
• Subjects: Disease Progression; Europe - epidemiology; European Continental Ancestry Group - ethnology; European Continental Ancestry Group - genetics; Female; Genetic Predisposition to Disease; Humans; Interleukin-6 - genetics; Male; Polymorphism, Single Nucleotide; Scleroderma, Systemic - ethnology; Scleroderma, Systemic - genetics; Europe
• ISSN: 0315-162X
• DOI: 10.3899/jrheum.120506

Systemic sclerosis (SSc) is a genetically complex autoimmune disease; the genetic component has not been fully defined. Interleukin 6 (IL-6) plays a crucial role in immunity and fibrosis, both key aspects of SSc. We investigated the influence of IL6 gene in the susceptibility and phenotype expression of SSc. We performed a large metaanalysis including a total of 2749 cases and 3189 controls from 6 white populations (Germany, The Netherlands, Norway, Spain, Sweden, and United Kingdom). Three IL6 single-nucleotide polymorphisms (SNP; rs2069827, rs1800795, and rs2069840) were selected by SNP tagging and genotyped using TaqMan(®) allele discrimination technology. Individual SNP metaanalysis showed no evidence of association of the 3 IL6 genetic variants with the global disease. Phenotype analyses revealed a significant association between the minor allele of rs2069840 and the limited cutaneous SSc clinical form (Bonferroni p = 0.036, OR 1.14, 95% CI 1.04-1.25). A trend of association between the minor allele of the rs1800795 and the diffuse cutaneous SSc clinical form was also evident (Bonferroni p = 0.072, OR 0.86, 95% CI 0.77-0.96). In the IL6 allelic combination analyses, the GGC allelic combination rs2069827-rs1800795-rs2069840 showed an association with overall SSc (Bonferroni p = 0.016, OR 1.13, 95% CI 1.04-1.23). Our results suggest that the IL6 gene may influence the development of SSc and its progression.