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Influence of the IL6 gene in susceptibility to systemic sclerosis

Publicado en:JOURNAL OF RHEUMATOLOGY. 39 (12): 2294-2302 - 2012-12-01 39(12), DOI: 10.3899/jrheum.120506

Autores: Cénit MC; Simeón CP; Vonk MC; Callejas-Rubio JL; Espinosa G; Carreira P; Blanco FJ; Narvaez J; Tolosa C; Román-Ivorra JA; Gómez-Garćia I; García-Hernández FJ; Gallego M; García-Portales R; Egurbide MV; Fonollosa V; De La Pẽna PG; López-Longo FJ; González-Gay MA; Hesselstrand R; Riemekasten G; Torsten W; Voskuyl AE; Schuerwegh AJ; Madhok R; Fonseca C; Denton C; Nordin A; Palm Ø; Van Laar JM; Hunzelmann N; Distler JHW; Kreuter A; Herrick A; Worthington J; Koeleman BP; Radstake TRDJ; Martiń J; Ortego-Centeno N; Ríos R; Navarrete N; Camps MT; Fernández-Nebro A; González-Escribano MF; Sánchez-Román J; Castillo MJ; Ángeles Aguirre M; Fernández-Gutiérrez B; Rodríguez-Rodríguez L; Vicente E; Andreu JL; De Castro MF; Martínez L; Castellví I; Pros A; Carballeira MR; Mejías RL; Díaz B; Trapiella L; Freire MDC; Vaqueiro I; Sáez-Comet L; Díaz F; Hernández V; Beltrán E; Robles MA; Oreiro N

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Resumen

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® 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. The Journal of Rheumatology Copyright © 2012. All rights reserved.

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