Dataset Information

The Clinical Significance of Interleukin-1 Receptor Antagonist +2018 Polymorphism in Rheumatoid Arthritis.

ABSTRACT:

Objective

Interleukin-1 receptor antagonist (IL-1Ra) acts as an inhibitor of IL-1; which is one of the culprit cytokines in rheumatoid arthritis (RA). Although +2018 polymorphism of IL-1Ra has been implicated in the pathogenesis of RA, its importance remains poorly understood. Hence, the purpose of this study was to determine the clinical significance of interleukin-1 receptor antagonist (IL-1Ra) +2018 polymorphism in RA.

Methods

Polymerase chain reaction (PCR) and sequencing were used to determine the genotypes of the IL-1Ra +2018 for 77 RA patients and 18 healthy controls. All RA patients were assessed for the disease activity score that includes 28 joints (DAS28) and radiographic disease damage based on Modified Sharp Score (MSS).

Results

The frequency of the T/T and C/T genotypes did not differ significantly (p = 0.893) between the RA patients and the controls. The C/T genotype had significantly higher mean disease activity (DAS 28) and disease damage (MSS) scores with p values of 0.017 and 0.004, respectively. Additionally, the ESR (erythrocyte sedimentation rate), CRP (C-reactive protein), the number of swollen and tender joints were higher for the C/T individuals. On multivariate analysis the CRP, swollen joint count and MSS remained significant with the following p values i.e. 0.045, 0.046 and less than 0.05.

Conclusions

C/T genotype of IL-1Ra +2018 prognosticates more aggressive disease in RA.

SUBMITTER: Ismail E

PROVIDER: S-EPMC4841519 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

The Clinical Significance of Interleukin-1 Receptor Antagonist +2018 Polymorphism in Rheumatoid Arthritis.

Ismail Endom E Nofal Omimah Khaled Jaber OK Sakthiswary Rajalingham R Shaharir Syahrul Sazliyana SS Sridharan Radhika R

PloS one 20160422 4

<h4>Objective</h4>Interleukin-1 receptor antagonist (IL-1Ra) acts as an inhibitor of IL-1; which is one of the culprit cytokines in rheumatoid arthritis (RA). Although +2018 polymorphism of IL-1Ra has been implicated in the pathogenesis of RA, its importance remains poorly understood. Hence, the purpose of this study was to determine the clinical significance of interleukin-1 receptor antagonist (IL-1Ra) +2018 polymorphism in RA.<h4>Methods</h4>Polymerase chain reaction (PCR) and sequencing were ...[more]

PMID: 27105431

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Project description:ObjectivesRheumatoid arthritis is a chronic inflammatory autoimmune disease. This study aimed to determine the association of interleukin-17A-197G/A polymorphism with rheumatoid arthritis in Sudanese patients.MethodsA case-control study was conducted between March and December 2018. Clinical and demographic data of the study participants were collected and analyzed. Polymerase chain reaction restriction fragment length polymorphism molecular technique was done to investigate interleukin-17A-197G/A polymorphisms. All statistical tests were considered statistically significant when p < 0.05.ResultsThe study population included 266 participants aged between 1 and 85 years, with an average of 40 years, classified into 85 (31.2%) cases (mean age 48.5 ± 11.3 years), and 181 (68.8%) controls (mean age 35.3 ± 15.9 years). The interleukin-17A homozygote AA genotype was more frequent among the control group compared to the case group; 95 (52.5%) and 7 (8.2%), respectively. The homozygote GG and the heterozygote AG genotypes were proportionally not different among the cases and control groups; 13 (54.2%) and 11 (45.8%), and 65 (46.4%) and 75 (53.6%), respectively. According to the distribution of interleukin-17A genotypes, a statistically significant difference was observed among cases with the interleukin-17A AA and AG genotypes, p values 0.001 and 0.004, respectively. For the association interleukin-17A genotypes and family history a negatively significant association was reported (95% confidence interval, -0.219, p value = 0.001). There was also a negatively significant association of interleukin-17A genotypes and anti-cyclic citrullinated peptide (95% confidence interval, -0.141, p value = 0.002).ConclusionThis study is the first study in Sudan established the association between interleukin-17A-197G/A (rs2275913) polymorphisms and susceptibly to rheumatoid arthritis. These findings appeal for further research in Sudan to investigate the exact role of IL-17A in immunopathology and disease severity among Sudanese rheumatoid arthritis.

Project description:INTRODUCTION: There has been no report in the literature of a soluble form of interleukin (IL)-18 receptor ? (IL-18R?). In this study, we evaluated the levels and characteristics of soluble IL-18R? (sIL-18R?) in the sera of patients with rheumatoid arthritis (RA) and compared these results to control populations. METHODS: The sIL-18R? complex was isolated from pooled human blood serum using an anti-IL-18R? monoclonal antibody affinity column. The purified sIL-18R? was then examined using Western blot analysis and used in experiments to evaluate the effects on an IL-18-responsive natural killer (NK) human cell line, NK0. An enzyme-linked immunosorbent assay was developed, and sera from 145 patients with RA, 6 patients with adult-onset Still's disease, 31 patients with osteoarthritis (OA), 39 patients with systemic lupus erythematosus (SLE) and 67 controls were tested, along with levels of immunoglobulin M, rheumatoid factor, anticyclic citrullinated peptide antibody, IL-18, IL-13 and interferon (IFN)-?. Area under the receiver operating characteristic curve (ROC-AUC) analysis was used to evaluate the diagnostic utility of the sIL-18R? complex. RESULTS: The isolated sIL-18R? complex can be associated with IL-18 and the soluble form of the IL-18R? chain. The sIL-18R? complex bound to the surface to the NK0 cell line, antagonized the stimulatory effects of IL-18 and IL-2 on the NK0 cell line and inhibited IFN-? production by the cells. The serum levels of sIL-18R? complex in RA (186.0 ± 33.5 ng/mL, n = 145) and adult-onset Still's disease (98.2 ± 8.9 ng/mL, n = 6) were significantly (P < 0.001) higher than those in the healthy controls (52.3 ± 8.5 ng/mL, n = 67), OA (38.6 ± 5.4 ng/mL, n = 31), SLE (44.6 ± 3.2 ng/mL, n = 39). The serum level of sIL-18R? complex was not significantly different between RA and adult-onset Still's disease patients. The serum levels of IL-18, IL-13 and IFN-? in the RA patients were significantly (P < 0.01) higher than in OA and SLE patients as well as healthy controls. ROC-AUC analysis of the serum concentration of sIL-18R? indicated that it was significantly diagnostic of RA. Moreover, a tumor necrosis factor inhibitor, etanercept, significantly (P < 0.0001) decreased levels of sIL-18R? in the sera of 29 RA patients 6 months after treatment. CONCLUSIONS: The sIL-18R? complex could be a potentially useful biomarker for the diagnosis of RA.

Dataset Information

The Clinical Significance of Interleukin-1 Receptor Antagonist +2018 Polymorphism in Rheumatoid Arthritis.

Objective

Methods

Results

Conclusions

Publications

The Clinical Significance of Interleukin-1 Receptor Antagonist +2018 Polymorphism in Rheumatoid Arthritis.

Similar Datasets

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