Carmen Cenit, Maria, Simeon, Carmen P., Vonk, Madelon C., Callejas-Rubio, Jose L., Espinosa, Gerard ORCID: 0000-0003-1336-0163, Carreira, Patricia, Blanco, Francisco J. ORCID: 0000-0001-9821-7635, Narvaez, Javier ORCID: 0000-0002-1614-8064, Tolosa, Carlos, Roman-Ivorra, Jose A., Gomez-Garcia, Inmaculada, Garcia-Hernandez, Francisco J., Gallego, Maria, Garcia-Portales, Rosa, Victoria Egurbide, Maria, Fonollosa, Vicente, Garcia de la Pena, Paloma, Lopez-Longo, Francisco J., Gonzalez-Gay, Miguel A. ORCID: 0000-0002-7924-7406, Hesselstrand, Roger, Riemekasten, Gabriela, Witte, Torsten, Voskuyl, Alexandre E., Schuerwegh, Annemie J., Madhok, Rajan, Fonseca, Carmen, Denton, Christopher, Nordin, Annika ORCID: 0000-0003-1976-4679, Palm, Oyvind ORCID: 0000-0001-5395-0665, van Laar, Jacob M., Hunzelmann, Nicolas, Distler, Joerg H. W., Kreuter, Alexander, Herrick, Ariane ORCID: 0000-0003-4941-7926, Worthington, Jane ORCID: 0000-0003-0544-042X, Koeleman, Bobby P., Radstake, Timothy R. D. J. and Martin, Javier ORCID: 0000-0002-2202-0622 (2012). Influence of the IL6 Gene in Susceptibility to Systemic Sclerosis. J. Rheumatol., 39 (12). S. 2294 - 2303. TORONTO: J RHEUMATOL PUBL CO. ISSN 1499-2752

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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)

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Carmen Cenit, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simeon, Carmen P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vonk, Madelon C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Callejas-Rubio, Jose L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Espinosa, GerardUNSPECIFIEDorcid.org/0000-0003-1336-0163UNSPECIFIED
Carreira, PatriciaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blanco, Francisco J.UNSPECIFIEDorcid.org/0000-0001-9821-7635UNSPECIFIED
Narvaez, JavierUNSPECIFIEDorcid.org/0000-0002-1614-8064UNSPECIFIED
Tolosa, CarlosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roman-Ivorra, Jose A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gomez-Garcia, InmaculadaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garcia-Hernandez, Francisco J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gallego, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garcia-Portales, RosaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Victoria Egurbide, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fonollosa, VicenteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garcia de la Pena, PalomaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lopez-Longo, Francisco J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gonzalez-Gay, Miguel A.UNSPECIFIEDorcid.org/0000-0002-7924-7406UNSPECIFIED
Hesselstrand, RogerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Riemekasten, GabrielaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Witte, TorstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Voskuyl, Alexandre E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schuerwegh, Annemie J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Madhok, RajanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fonseca, CarmenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Denton, ChristopherUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nordin, AnnikaUNSPECIFIEDorcid.org/0000-0003-1976-4679UNSPECIFIED
Palm, OyvindUNSPECIFIEDorcid.org/0000-0001-5395-0665UNSPECIFIED
van Laar, Jacob M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hunzelmann, NicolasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Distler, Joerg H. W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kreuter, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herrick, ArianeUNSPECIFIEDorcid.org/0000-0003-4941-7926UNSPECIFIED
Worthington, JaneUNSPECIFIEDorcid.org/0000-0003-0544-042XUNSPECIFIED
Koeleman, Bobby P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Radstake, Timothy R. D. J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martin, JavierUNSPECIFIEDorcid.org/0000-0002-2202-0622UNSPECIFIED
URN: urn:nbn:de:hbz:38-477468
DOI: 10.3899/jrheum.120506
Journal or Publication Title: J. Rheumatol.
Volume: 39
Number: 12
Page Range: S. 2294 - 2303
Date: 2012
Publisher: J RHEUMATOL PUBL CO
Place of Publication: TORONTO
ISSN: 1499-2752
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
SOLUBLE IL-6 RECEPTOR; PROMOTER POLYMORPHISM; INTERLEUKIN-6 IL-6; SERUM-LEVELS; ONCOSTATIN M; SCLERODERMA; SKIN; PATHOGENESIS; ASSOCIATION; MECHANISMSMultiple languages
RheumatologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/47746

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