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- DOI: 10.3899/jrheum.120506
- PMID: 23027890
- UKPMCID: 23027890
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Influence of the IL6 Gene in Susceptibility to Systemic Sclerosis.
CĂ©nit, Maria Carmen; SimeĂłn, Carmen P; Vonk, Madelon C; Callejas-Rubio, Jose L; Espinosa, Gerard; Carreira, Patricia; Blanco, Francisco J; Narvaez, Javier; Tolosa, Carlos; Román-Ivorra, JosĂ© A; GĂłmez-GarcĂa, Inmaculada; GarcĂa-Hernández, Francisco J; Gallego, MarĂa; GarcĂa-Portales, Rosa; Egurbide, MarĂa Victoria; Fonollosa, Vicente; de la Peña, Paloma GarcĂa; LĂłpez-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, Oyvind; van Laar, Jacob M; Hunzelmann, Nicolas; Distler, Jörg H W; Kreuter, Alexander; Herrick, Ariane; Worthington, Jane; Koeleman, Bobby P; Radstake, Timothy R D J; MartĂn, Javier
The Journal of rheumatology. 2012;39(12):2294-2302.
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Full-text held externally
- DOI: 10.3899/jrheum.120506
- PMID: 23027890
- UKPMCID: 23027890
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® 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.
Bibliographic metadata
- CĂ©nit, Maria Carmen
- SimeĂłn, Carmen P
- Vonk, Madelon C
- Callejas-Rubio, Jose L
- Espinosa, Gerard
- Carreira, Patricia
- Blanco, Francisco J
- Narvaez, Javier
- Tolosa, Carlos
- Román-Ivorra, José A
- GĂłmez-GarcĂa, Inmaculada
- GarcĂa-Hernández, Francisco J
- Gallego, MarĂa
- GarcĂa-Portales, Rosa
- Egurbide, MarĂa Victoria
- Fonollosa, Vicente
- de la Peña, Paloma GarcĂa
- LĂłpez-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, Oyvind
- van Laar, Jacob M
- Hunzelmann, Nicolas
- Distler, Jörg H W
- Kreuter, Alexander
- Herrick, Ariane
- Worthington, Jane
- Koeleman, Bobby P
- Radstake, Timothy R D J
- MartĂn, Javier