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Influence of the IL6 Gene in Susceptibility to Systemic Sclerosis

Lookup NU author(s): Professor Jaap Van Laar

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Abstract

Objective. 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. Methods. 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 (R) allele discrimination technology. Results. 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). Conclusion. Our results suggest that the IL6 gene may influence the development of SSc and its progression. (First Release Oct 1 2012; J Rheumatol 2012;39:2294-302; doi:10.3899/jrheum.120506)


Publication metadata

Author(s): Cenit MC, Simeon CP, Vonk MC, Callejas-Rubio JL, Espinosa G, Carreira P, Blanco FJ, Narvaez J, Tolosa C, Roman-Ivorra JA, Gomez-Garcia I, Garcia-Hernandez FJ, Gallego M, Garcia-Portales R, Egurbide MV, Fonollosa V, de la Pena PG, Lopez-Longo FJ, Gonzalez-Gay MA, Hesselstrand R, Riemekasten G, Witte T, Voskuyl AE, Schuerwegh AJ, Madhok R, Fonseca C, Denton C, Nordin A, Palm O, van Laar JM, Hunzelmann N, Distler JHW, Kreuter A, Herrick A, Worthington J, Koeleman BP, Radstake TRDJ, Martin J, Spanish Scleroderma Grp

Publication type: Article

Publication status: Published

Journal: Journal of Rheumatology

Year: 2012

Volume: 39

Issue: 12

Pages: 2294-2302

Print publication date: 01/10/2012

ISSN (print): 0315-162X

ISSN (electronic): 1499-2752

Publisher: Journal of Rheumatology Publishing Co. Ltd.

URL: http://dx.doi.org/10.3899/jrheum.120506

DOI: 10.3899/jrheum.120506


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Funding

Funder referenceFunder name
GEN-FER from the Spanish Society of Rheumatology
RETICS Program
European League Against Rheumatism
CTS-180Junta de Andalucia
PI-0590-2010Consejeria de Salud, Junta de Andalucia
RD08/0075Instituto de Salud Carlos III (ISCIII), Spain, within the VI PN de I+D+i
SAF2009-11110Spanish Ministry of Science

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