Association of interleukin‐6 and interleukin‐10 genotypes with radiographic damage in rheumatoid arthritis is dependent on autoantibody status
Open Access
- 30 July 2007
- journal article
- research article
- Published by Wiley in Arthritis & Rheumatism
- Vol. 56 (8), 2549-2556
- https://doi.org/10.1002/art.22814
Abstract
Objective Recent evidence has highlighted a major genetic contribution to radiographic damage in rheumatoid arthritis (RA). The objective of this study was to determine whether genetic variants in the loci for interleukin‐1 (IL‐1), IL‐6, IL‐10, protein tyrosine phosphatase N22 (PTPN22), and selenoprotein S are associated with radiographic damage. Methods Modified Larsen scores of radiographic damage were determined in a cross‐sectional population of patients with RA (n = 964). Rheumatoid factor (RF) and anti–cyclic citrullinated peptide (anti‐CCP) were also assayed. The Kruskal‐Wallis nonparametric test was used to compare median radiographic damage scores across genotype groups, followed by the Cuzick nonparametric test for trend to assess gene‐dose effects. Results An allele‐dose association of IL‐6 −174G with increasing radiographic damage was present (P = 0.005), but only in patients who were RF positive (P = 0.004) or anti‐CCP positive (P = 0.01). Patients with the IL‐10 −592CC genotype had more extensive radiographic damage than did those with the AC or AA genotype (P = 0.006), but this was observed only among patients who were RF negative (P = 0.002) or anti‐CCP negative (P = 0.002). However, RF status and anti‐CCP status were not associated with the IL‐6 or IL‐10 genotype. No other genetic associations were detected, apart from a marginal association of PTPN22 +1858T with increased radiographic damage. Conclusion The reported associations of IL‐6 −174G with high IL‐6 production and IL‐10 −592 with low IL‐10 production and our own results support a role of genetically determined dysregulated cytokine production in disease severity. The lack of association of these genotypes with RF and anti‐CCP antibody status suggests that they act downstream of autoantibody production. We conclude that IL‐6 and IL‐10 genotypes may be useful in predicting disease severity in autoantibody‐positive and autoantibody‐negative patients, respectively.Keywords
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