Abstract
ObjectiveRecent 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.MethodsModified 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.ResultsAn 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.ConclusionThe 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.
Highlights
We conclude that IL-6 and IL-10 genotypes may be useful in predicting disease severity in autoantibodypositive and autoantibody-negative patients, respectively
Recent evidence has implicated the common allele of the R620W single-nucleotide polymorphism (SNP) in the hematopoietic-specific protein tyrosine kinase, protein tyrosine phosphatase N22 (PTPN22), with susceptibility to several autoimmune diseases, including rheumatoid arthritis (RA) [4]
We examined whether SNPs in IL-1, IL-6, IL-10, PTPN22, and selenoprotein S (SEPS) are associated with radiographic damage in a large cross-sectional cohort of patients with RA, and determined whether the associations detected were independent of production of rheumatoid factor (RF) and anti-CCP
Summary
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
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have