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A gain of function polymorphism in the interleukin-6 receptor influences RA susceptibility

Marinou, I., Walters, K. and Wilson, A.G. (2010) A gain of function polymorphism in the interleukin-6 receptor influences RA susceptibility. Annals of the Rheumatic Diseases, 69. pp. 1191-1194.

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Abstract

Objectives: To investigate the possible role of a functional polymorphism in the interleukin-6 receptor (sIL-6R) gene in the genetic background of rheumatoid arthritis (RA).

Methods: We tested for association between disease status and of the sIL-6R rs8192284 (A358D) variant in 965 RA patients and 988 unrelated healthy controls. Odds ratios (OR) for disease were calculated with asymptotic 95% confidence intervals (95% CI); p-values less than 0.05 were considered statistically significant after adjustment for multiple testing. To determine the relationship between protein levels and IL-6R A358D genotype we measured the protein levels of sIL-6R in 100 plasma samples from healthy controls using an enzyme-linked immunosorbant assay (ELISA) and compared them across the genotype groups.

Results: The allele frequency of the C allele (alanine) was lower in cases compared with controls (38.4% and 41.7% respectively, p=0.04, OR=0.9, CI= 0.8-1.0) as were the CC/AC genotypes compared to AA genotype frequencies(61.0% in RA cases vs 67.5% in controls, p=0.004, OR=0.8, 95% CI=0.6-0.9). Plasma levels of sIL-6R differed significantly according to genotype in the controls: 17.00 ± 2.03 ng/ml for A/A, 20.08 ± 1.83 for A/C and 21.57 ± 2.10 for C/C (p = 0.0001).

Conclusion: These data suggest a role for genetically determined lower sIL-6R levels as being a risk factor for RA. The pro-inflammatory role of the IL-6 system in established RA has been highlighted by the used of anti-sIL-6R antibodies. Our data, however, suggest a protective effect of IL-6 on the risk of developing RA.

Item Type: Article
Institution: The University of Sheffield
Academic Units: The University of Sheffield > Faculty of Science (Sheffield) > School of Mathematics and Statistics (Sheffield)
The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine (Sheffield)
Depositing User: Mrs Megan Hobbs
Date Deposited: 17 Mar 2010 18:18
Last Modified: 01 May 2014 13:41
Published Version: http://dx.doi.org/10.1136/ard.2008.100644
Status: Published
Publisher: BMJ Publishing
Identification Number: 10.1136/ard.2008.100644
URI: http://eprints.whiterose.ac.uk/id/eprint/10692

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