Polymorphisms of Promoter Region of<i>TNF-α</i>Gene in Iranian Azeri Turkish Patients with Behçet’s Disease

Abdolmohammadi, Reza; Bonyadi, Mortaza

doi:10.3346/jkms.2017.32.1.33

Cited by 15 publications

(17 citation statements)

References 24 publications

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“…Except for IL-1 β (rs1143627) (36), these findings are in line with observations of Iranian investigations on autoimmune diseases (37, 38). Among four studied polymorphisms in TNF- α, our observation revealed that the prevalence of minor allele in rs1799724 is significantly higher in the patients than controls, confirming previously published date from Iran in inflammatory disease (39). However, this significance disappeared after correction for multiple analysis.…”

Section: Discussionsupporting

confidence: 90%

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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Section: Discussionsupporting

confidence: 90%

Proinflammatory Cytokine Gene Polymorphisms in Bullous Pemphigoid

et al. 2019

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“…In agreement with our data, Ates and collaborators reported no association of the polymorphism and both BS clinical hallmark and severity [23]. The polymorphism did not show any association with clinical findings also in Tukish population [22,25]. Lee and colleagues studied the SNP genotypes according to the presence of uveitis, recognising that the presence of rs1800629 in patients with uveitis were not different from those without uveitis [28].…”

Section: Genotyping Ofsupporting

confidence: 89%

“…Similarly to our investigation, several studies assessed the influence of the promoter polymorphism on the expression of TNF-α in BS or its susceptibility or its severity and clinical features, as well as its role as drug-response allele [14,[22][23][24][25][26][27][28][29][30][31][32]. The effect of geographical differences, rather than the high genetic variation, are important factors for the adaptability and the evolution of any population.…”

Section: Genotyping Ofmentioning

confidence: 99%

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Correlation of tumor necrosis factor-α -308G>A polymorphism with susceptibility, clinical manifestations and severity in Behçet syndrome: evidences from an Italian genetic case-control study

Padula

Leccese

Lascaro

et al. 2019

Preprint

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Background The tumor necrosis factor (TNF)α is a multifunctional proinflammatory cytokine, implicated in a variety of diseases, including Behçet syndrome (BS), a rare vasculitis with a wide spectrum of clinical manifestations. The aim of the present study was to investigate the association between a functional drug-response TNFα gene polymorphism (at the positions of -308; rs1800629) and both disease susceptibility and clinical manifestations in a cohort of Italian BS patients compared with healthy controls (HC).Methods We recruited 130 Italian patients with BS consecutively seen at Rheumatology Institute of Lucania (Italy) and 100 ethnically, age and gender matched HC. Demographic and clinical features were retrieved by medical records. Specific primer pairs were designed for TNFα coverage. Genomic DNA isolation, primer-specific PCR amplification and direct sequencing were performed for genotyping our group of patients and controls. In silico analysis was downstream performed using Mutation Surveyor software (SoftGenetics, USA) and NCBI-BlastN on line tool for the query-subject similarity analysis.Results The genotype distribution of BS patients and HC underlined a higher percentage of wild-type GG genotype in BS patients group vs HC (106/130 patients, 81.5% vs 91/100 HC, 91%; p<0.05), while the heterozygous genotype (GA) was identified in 24/130 patients (18.5%) vs 9/100 HC (9%) (p<0.05). GA genotype was significantly associated with the disease (OR=2.29, 95% CI 1.01-5.18). No significant association was recognized between the SNP and the BS clinical manifestations, as well as with disease severity (Krause's index).Conclusions We found statistically significant higher frequency of TNFα rs1800629 GA genotype in patients than in controls. No significant association was recognized between the polymorphism and the clinical parameters, as well as between the SNP and the disease severity. Our data need to be confirmed in larger cohort of patients and matched controls.

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“…Recently, one new study was published confirming the association between Iranian BD patients and the 857T/C polymorphism [52]. Therefore, there is evidence for a genetic background for the overproduction of TNF-α in BD.…”

Section: Genetics Of Bdmentioning

confidence: 96%

Behҫet’s Disease, and the Role of TNF-α and TNF-α Blockers

Houwen

Laar

2020

IJMS

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In this both narrative and systematic review, we explore the role of TNF-α in the immunopathogenesis of Behçet’s disease (BD) and the effect of treatment with TNF-α blockers. BD is an auto-inflammatory disease, characterized by recurrent painful oral ulcerations. The pathogenesis of BD is not yet elucidated; it is assumed that TNF-α may play a key role. In the narrative review, we report an increased production of TNF-α, which may be stimulated via TLR-signaling, or triggered by increased levels of IL-1β and IFN-γ. The abundance of TNF-α is found in both serum and in sites of inflammation. This increased presence of TNF-α stimulates T-cell development toward pro-inflammatory subsets, such as Th17 and Th22 cells. Treatment directed against the surplus of TNF-α is investigated in the systematic review, performed according to the PRISMA guideline. We searched the Pubmed and Cochrane database, including comparative studies only. After including 11 studies, we report a beneficial effect of treatment with TNF-α blockers on the various manifestations of BD. In conclusion, the pivotal role of TNF-α in the immunopathogenesis of BD is reflected in both the evidence of their pro-inflammatory effects in BD and in the evidence of the positive effect of treatment on the course of disease in BD.

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Polymorphisms of Promoter Region ofTNF-αGene in Iranian Azeri Turkish Patients with Behçet’s Disease

Cited by 15 publications

References 24 publications

Proinflammatory Cytokine Gene Polymorphisms in Bullous Pemphigoid

Proinflammatory Cytokine Gene Polymorphisms in Bullous Pemphigoid

Correlation of tumor necrosis factor-α -308G>A polymorphism with susceptibility, clinical manifestations and severity in Behçet syndrome: evidences from an Italian genetic case-control study

Behҫet’s Disease, and the Role of TNF-α and TNF-α Blockers

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Polymorphisms of Promoter Region ofTNF-αGene in Iranian Azeri Turkish Patients with Behçet’s Disease

Cited by 15 publications

References 24 publications

Proinflammatory Cytokine Gene Polymorphisms in Bullous Pemphigoid

Proinflammatory Cytokine Gene Polymorphisms in Bullous Pemphigoid

Correlation of tumor necrosis factor-α -308G&gt;A polymorphism with susceptibility, clinical manifestations and severity in Behçet syndrome: evidences from an Italian genetic case-control study

Behҫet’s Disease, and the Role of TNF-α and TNF-α Blockers

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Correlation of tumor necrosis factor-α -308G>A polymorphism with susceptibility, clinical manifestations and severity in Behçet syndrome: evidences from an Italian genetic case-control study