Article Text

other Versions

PDF
A gain of function polymorphism in the interleukin-6 receptor influences RA susceptibility
  1. I Marinou (mdp04im{at}sheffield.ac.uk)
  1. University of Sheffield, United Kingdom
    1. K Walters (k.walters{at}sheffield.ac.uk)
    1. University of Sheffield, United Kingdom
      1. J Winfield (kathryn.newton{at}sth.nhs.uk)
      1. University of Sheffield, United Kingdom
        1. D E Bax (d.e.bax{at}sheffield.ac.uk)
        1. University of Sheffield, United Kingdom
          1. A G Wilson (a.g.wilson{at}sheffield.ac.uk)
          1. University of Sheffield, United Kingdom

            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.

            Statistics from Altmetric.com

            Request permissions

            If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.