Dataset Information

Tumor Necrosis Factor Alpha Gene Polymorphism and Association With Its Serum Level in Iranian Population with Rheumatoid Arthritis.

ABSTRACT: Objectives:This study aims to determine whether promoter -238 G/A polymorphism in tumor necrosis factor-alpha (TNF-?) gene is associated with susceptibility to rheumatoid arthritis (RA) in Iranian population and serum level of TNF-a. Patients and methods:This case-controlled study was performed on two groups including 90 RA patients (20 males, 70 females; mean age 50.3 years; range 26 to 65 years) and 90 healthy controls (21 males, 69 females; mean age 48.6 years; range 27 to 63 years). We determined the frequency of -238 G/A TNF-a gene polymorphism by polymerase chain reaction restriction fragment length polymorphism. We measured the serum level of TNF-a using enzyme-linked immunosorbent assay method. Also, we determined the association of serum TNF-a level with the polymorphism in RA patients. Results:There was no significant difference in terms of sex and age in the two groups. In the RA group, the genotype frequency of -238 G/A polymorphism was GG (76.6%), GA (17.8%), and AA (5.6%). In the control group, the genotype frequency of -238 G/A polymorphism was GG (83.5%), GA (8.8%), and AA (7.7%). Statistical analysis showed no significant difference in the genotype frequency of this polymorphism between two groups (p=0.07). The serum level of TNF-a were 5.21±1.69 Pg/mL (range 0 to 11.6) in the control group and 62.4±27.1 Pg/mL (range 0 to 117.22) in the RA group (p<0.0001). There was no significant difference in terms of serum TNF-a level and different genotypes in the RA group (p=0.5). Conclusion:Our findings demonstrate that the TNF-a -238 G/A gene polymorphism may not represent a significant risk factor for RA in Iranian population and there is no association between the polymorphism and serum TNF-a level in RA patients.

SUBMITTER: Hadinedoushan H

PROVIDER: S-EPMC6190968 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Tumor Necrosis Factor Alpha Gene Polymorphism and Association With Its Serum Level in Iranian Population with Rheumatoid Arthritis.

Hadinedoushan Hossein H Noorbakhsh Parisa P Soleymani-Salehabadi Hossein H

Archives of rheumatology 20160727 4

<h4>Objectives</h4>This study aims to determine whether promoter -238 G/A polymorphism in tumor necrosis factor-alpha (TNF-α) gene is associated with susceptibility to rheumatoid arthritis (RA) in Iranian population and serum level of TNF-a.<h4>Patients and methods</h4>This case-controlled study was performed on two groups including 90 RA patients (20 males, 70 females; mean age 50.3 years; range 26 to 65 years) and 90 healthy controls (21 males, 69 females; mean age 48.6 years; range 27 to 63 y ...[more]

PMID: 30375554

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Project description:Background: This study aimed to investigate the molecular mechanism of Radix Paeoniae Alba (white peony, WP) in treating immune inflammatory diseases of rheumatoid arthritis (RA) and tumor necrosis factor-alpha (TNF-α) inhibitors (TNFis) by using network pharmacology and molecular docking. Methods: In this study, the ingredient of WP and the potential inflammatory targets of RA were obtained from the Traditional Chinese Medicine Systematic Pharmacology Database, GeneCard, and OMIM databases, respectively. The establishment of the RA-WP-potential inflammatory target gene interaction network was accomplished using the STRING database. Network maps of the WP-RA-potential inflammatory target gene network were constructed using Cytoscape software. Gene ontology (GO) and the biological pathway (KEGG) enrichment analyses were used to further explore the RA mechanism and therapeutic effects of WP. Molecular docking technology was used to analyze the optimal effective components from WP for docking with TNF-α. Results: Thirteen active ingredients and 71 target genes were screened from WP, and 49 of the target genes intersected with RA target inflammatory genes and were considered potential therapeutic targets. Network pharmacological analysis showed that the WP active ingredients such as mairin, DPHCD, (+)-catechin, beta-sitosterol, paeoniflorin, sitosterol, and kaempferol showed better correlation with RA inflammatory target genes such as PGR, PTGS1, PTGS2, NR3C2, TNFSF15, and CHRM2, respectively. The immune-inflammatory signaling pathways of the active ingredients for the treatment of RA are the TNF-α signaling pathway, Toll-like receptor signaling pathway, cell apoptosis, interleukin-17 signaling pathway, C-type lectin receptor signaling pathway, mitogen-associated protein kinase, etc. Molecular docking results suggested that mairin was the most appropriate natural TNFis. Conclusion: Our findings provide an essential role and basis for further immune-inflammatory studies into the molecular mechanisms of WP and TNFis development in RA.

Project description:OBJECTIVE:Anti-tumor necrosis factor alpha (anti-TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). The aim of the present study was to test established RA genetic risk factors to determine whether the same alleles also influence the response to anti-TNF therapy. METHODS:A total of 1,283 RA patients receiving etanercept, infliximab, or adalimumab therapy were studied from among an international collaborative consortium of 9 different RA cohorts. The primary end point compared RA patients with a good treatment response according to the European League Against Rheumatism (EULAR) response criteria (n = 505) with RA patients considered to be nonresponders (n = 316). The secondary end point was the change from baseline in the level of disease activity according to the Disease Activity Score in 28 joints (triangle upDAS28). Clinical factors such as age, sex, and concomitant medications were tested as possible correlates of treatment response. Thirty-one single-nucleotide polymorphisms (SNPs) associated with the risk of RA were genotyped and tested for any association with treatment response, using univariate and multivariate logistic regression models. RESULTS:Of the 31 RA-associated risk alleles, a SNP at the PTPRC (also known as CD45) gene locus (rs10919563) was associated with the primary end point, a EULAR good response versus no response (odds ratio [OR] 0.55, P = 0.0001 in the multivariate model). Similar results were obtained using the secondary end point, the triangle upDAS28 (P = 0.0002). There was suggestive evidence of a stronger association in autoantibody-positive patients with RA (OR 0.55, 95% confidence interval [95% CI] 0.39-0.76) as compared with autoantibody-negative patients (OR 0.90, 95% CI 0.41-1.99). CONCLUSION:Statistically significant associations were observed between the response to anti-TNF therapy and an RA risk allele at the PTPRC gene locus. Additional studies will be required to replicate this finding in additional patient collections.

Dataset Information

Tumor Necrosis Factor Alpha Gene Polymorphism and Association With Its Serum Level in Iranian Population with Rheumatoid Arthritis.

Publications

Tumor Necrosis Factor Alpha Gene Polymorphism and Association With Its Serum Level in Iranian Population with Rheumatoid Arthritis.

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