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Interleukin (IL) 1α, IL1β, IL receptor antagonist, and IL10 polymorphisms in psoriatic arthritis
  1. L Peddle,
  2. C Butt,
  3. T Snelgrove,
  4. P Rahman
  1. Memorial University of Newfoundland, St Clare’s Mercy Hospital, Memorial University of Newfoundland, St John’s Newfoundland, Canada
  1. Correspondence to:
    Dr P Rahman
    St Clare’s Mercy Hospital, 1 South - 154 LeMarchant Rd, St John’s, Newfoundland, Canada A1C-5B8; prahmanmun.ca

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Interleukin (IL) 1 is a potent proinflammatory cytokine that occurs as IL1α and IL1β. The biological activity of IL1α and IL1β is initiated by binding with type 1 IL1 receptor and is inhibited by IL1 receptor antagonist (ILRa).1 IL10 is an anti-inflammatory cytokine that suppresses macrophage production of cytokines and enhances soluble cytokine receptor release.2 These cytokines have been implicated in the pathogenesis of psoriatic arthritis (PsA), as increased expression of IL1 and IL10 has been observed in the synovial fluid and synovial membrane of patients with PsA in comparison with patients with osteoarthritis.3 Given the proposed function of these cytokines in autoimmune disease, we set out to examine the role of polymorphisms in IL1α, IL1β, ILRa, and IL10 in the Newfoundland PsA population.

This study was approved by the ethics committee at the Memorial University of Newfoundland. In this study, PsA was defined as an inflammatory arthritis in patients with psoriasis and the absence of other causes for inflammatory arthritis. Patients and controls were genotyped for the following single nucleotide polymorphisms (SNPs): IL1α (−889; rs1143634), IL1β (+3953; rs1800587), and IL10 (−1082; rs1800896) using the Sequenom MassArray platform. All primers were designed using SpectroDESIGNER software. For ILRa (accession No AF387734), an 86 bp variable number tandem repeat was determined by a polymerase chain reaction.

Two hundred and twenty six patients with PsA and 95 matched controls were studied. The mean age of the patients with PsA was 54.0 years; 108 (48%) were women. All genotypes satisfied the Hardy-Weinberg equilibrium. χ2 Tests were used to examine the relationship between the minor allele frequencies of the candidate genes and PsA. The minor allele frequencies for patients with PsA and controls were for IL1α (T) 0.24 v 0.31 (odds ratio 0.7 (95% confidence interval 0.4 to 1.2)) respectively; for IL1β (T) 0.24 v 0.25 (0.9 (0.5 to 1.6)); for ILRa (two repeats) 0.27 v 0.24 (1.1 (0.7 to 2.0)); and for IL10 (A) 0.47 v 0.49 (0.9, (0.5 to 1.6)). Thus none of the polymorphisms examined were significantly associated with PsA in the Newfoundland population.

There is a paucity of association studies of IL1 and IL10 in PsA. In studies with an admixed white population Ravindran et al noted an increased frequency of the IL1α −889 polymorphism among patients with PsA but observed no difference for IL1β +3953 and IL1 receptor R1 +970 genes.4 Another study demonstrated no association between IL1β +3953 and IL1Ra gene polymorphisms in patients with PsA nor with IL10 SNPs (−1082 and −592) and PsA.5

Newfoundland has a white founder population known to exhibit homogeneity comparable to that of the Hutterites.6 A potential advantage in studying this population is the detection of small to modest genetic effects, as a result of an enhanced signal to noise ratio. In our study no association was found between polymorphisms in IL1α (−889), IL1β (+3953), IL10 (−1082), and ILRa in the Newfoundland founder population. Thus, these polymorphisms are unlikely to have a major role in the Newfoundland PsA population. We cannot, however, rule out the possibility that an association with other SNPs exists in these genes. Furthermore, we also acknowledge that because our sample size is limited we are unlikely to detect small differences in allele frequencies.

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