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

Hadinedoushan, Hossein; Noorbakhsh, Parisa; Soleymani-Salehabadi, Hossein

doi:10.5606/archrheumatol.2016.5907

Cited by 13 publications

(6 citation statements)

References 43 publications

(41 reference statements)

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“…[47] showed no significant difference (p>0.05) in TNF-α protein levels in RA patients between -308 GG and AA or GA genotypes. Similarly, we also concurred with [12] and [48] findings, who demonstrated no relationship between the -308, -238 G/A polymorphism and serum TNF-α levels in Iraqi and Iranian RA patients, respectively. Our findings, on the other hand, contradicted the findings of [49], who discovered that the -308 GA/AA genotype was related with elevated TNF-α levels.…”

Section: Discussionsupporting

confidence: 92%

Biogenetic Markers for Predicting Response to Immunotherapy in Rheumatoid Arthritis

Jabbar

Mohammed²,

Ali³

2023

EJBIOMED

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Background: TNF-α plays a critical role in the pathogenesis of RA. Gene polymorphisms occurring in this pro-inflammatory cytokine or their receptors may influence responses to biological therapy. Objectives: This study aimed to evaluate the impact of -238G/A(rs361525), -308G/A(rs1800629), -376G/A(rs1800750), +489G/A(rs80267059) SNPs in TNF-α and +587T/G(rs1061622), +884A/G(rs5746032) SNPs in TNFRII genes on responsiveness to TNF inhibitors as well as their effect on serum levels of TNF-α and TNFRII. Subjects and methods: Sixty patients with RA treated with anti-TNF therapy (30 responders and 30 non-responders) were allocated to this study. SNPs in the TNF-α and TNFRII genes were studied by three different techniques: PCR-sequencing, PCR-RFLP, and q-PCR-TaqMan assay. TNF-α and TNFRII serum levels were determined using the ELISA technique. Results: TNF-α -308 (GA), +489 (GA), and TNFRII +587 (TG) genotypes were found to be more associated with non-responsiveness to TNF than homozygous genotypes (OR: 1.3, 2.5, and 2.0, respectively). On other hand, TNF-α -238 and -376 (GA) genotypes, were found to be more associated with TNFi responsiveness than homozygous genotypes (OR: 0.172 and 0.22, respectively). However, none of them reached a significant level. Furthermore, the studied SNPs were found to be unrelated to serum levels of TNF-α and TNFRII. Conclusion: According to our findings, the TNF-α -238G/A, -308G/A, -376G/A, +489G/A, and TNFRII +587T/G, +884A/G SNPs were not significantly associated with the responsiveness of RA patients to biological therapy and had no effect on the serum levels of TNF-α and TNFR.

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Section: Discussionsupporting

confidence: 92%

Biogenetic Markers for Predicting Response to Immunotherapy in Rheumatoid Arthritis

Jabbar

Mohammed²,

Ali³

2023

EJBIOMED

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“…However, this significance disappeared after correction for multiple analysis. Similar to reported findings from Iran on autoimmune or inflammatory diseases, no significant differences were observed in our cohort study in all other SNPs in TNF- α (40–42).…”

Section: Discussionsupporting

confidence: 91%

Proinflammatory Cytokine Gene Polymorphisms in Bullous Pemphigoid

et al. 2019

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Bullous pemphigoid (BP) is a rare autoimmune skin blistering disease, characterized by the presence of autoantibodies against hemidesmosomal autoantigens. Cytokine expression is altered in BP patients, and several of these differently expressed cytokines, including IL-1α, IL-1β, IL-8, and TNF-α, contribute to disease pathogenesis. Since genetic polymorphisms in the genes of these cytokines might be implicated in susceptibility to BP disease, we aimed at testing this implication in susceptibility to BP in an Iranian cohort. Blood samples were collected from the subjects and genomic DNA was extracted. To detect the single nucleotide polymorphisms (SNPs), IL-1 α (rs1800587), IL-1 β (rs1143627, rs16944, rs1143634), IL-8 (rs4073), and TNF- α (rs1799964, rs1800630, rs1799724, and rs361525) genes were genotyped in BP patients and healthy controls as well as IL-8 (rs4073) in pemphigus vulgaris (PV) patients. Quantitative gene expression was evaluated by RT-PCR analysis. A significant difference was observed in the distribution of genotypes or alleles of IL-8 SNP between the BP patients and controls. The A-allele of IL-8 SNP is significantly more prevalent in the control individuals compared to the BP patient. To further validate this observation, we included PV patients as an additional control. Again, the A-allele of IL-8 SNP is significantly more prevalent in the PV compared to the BP patients. While we observed a trend toward significant differences regarding alleles of TNF- α rs1799724 as well as alleles of TNF- α rs1799964, this difference was, however, not evident after correction for multiple analysis. There was no significant difference in all other studied SNPs. In contrast to IL-1 α, IL-1 β, and TNF- α, IL-8 gene expression levels were significantly higher in the patients than that of controls. The minor allele in IL-8 SNP might play a protective role in susceptibility to BP in Iranian patients. Although higher expression levels of IL-8 gene was found in the patients compared with healthy controls, these levels, however, suggest no association with the examined polymorphism. Moreover, further investigation revealed an elevation in gene expression between wild and polymorphic genotypes of IL-1 α rs1800587 and TNF- α rs361525 in the patient group and these SNPs are therefore associated with altering the levels of gene expression.

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“…The following points need to be taken into consideration when interpreting our findings. First, previous experimental studies have found that TNF‐α , IL‐1 , or IL‐6 polymorphisms may alter the messenger RNA expression level of TNF‐α, IL‐1, and IL‐6 14,15 . Therefore, these polymorphisms may generate an imbalance status between Th1 and Th2 related immune responses, and ultimately influence the risk of asthma.…”

Section: Discussionmentioning

confidence: 99%

Associations of TNF‐α ‐238G/A, TNF‐α ‐308G/A, and IL‐6 ‐174G/C polymorphisms with the risk of asthma: Evidence from a meta‐analysis

Zhu

Zhang

Wang

et al. 2020

Pediatric Pulmonology

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Background: Previously, many genetic epidemiological studies have investigated associations between Th1-related cytokine polymorphisms and the risk of asthma, with inconsistent results. Accordingly, we carried out a meta-analysis to more precisely estimate associations between Th1-related cytokine polymorphisms and the risk of asthma. Methods: Systematic literature searching of Medline, Embase, Wanfang, VIP, and CNKI was conducted by the authors to identify eligible publications, and 69 genetic epidemiological studies were finally found to be eligible for quantitative analyses. Results: We found that genotypic frequencies of TNF-α-238G/A

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

Cited by 13 publications

References 43 publications

Biogenetic Markers for Predicting Response to Immunotherapy in Rheumatoid Arthritis

Biogenetic Markers for Predicting Response to Immunotherapy in Rheumatoid Arthritis

Proinflammatory Cytokine Gene Polymorphisms in Bullous Pemphigoid

Associations of TNF‐α ‐238G/A, TNF‐α ‐308G/A, and IL‐6 ‐174G/C polymorphisms with the risk of asthma: Evidence from a meta‐analysis

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