scholarly journals Tumor necrosis factor (TNF)-α gene +489 polymorphisms: association with psoriatic arthritis

2013 ◽  
Vol 86 (1) ◽  
Author(s):  
G. Murdaca ◽  
F. Puppo
Keyword(s):  
Psoriatic Arthritis ◽  
Tumor Necrosis Factor ◽  
Single Nucleotide Polymorphisms ◽  
Tumor Necrosis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Tnf Α ◽  
The Difference ◽  
Necrosis Factor

Objective of this work was to investigate the role of single nucleotide polymorphisms (SNPs) at position +489 of the tumor necrosis factor (TNF)-α gene in generic susceptibility and severity of psoriatic arthritis (PsA). Fifty-seven Caucasian PsA patients diagnosed according to CASPAR criteria and 155 healthy matched controls were studied. PASI score, DAS28 and Disability INdex HAQ were calculated. Genomic DNA was extracted from peripheral blood samples and SNPs +489 G>A (rs 80267959) were amplified by PCR. The SNP +489 genotype was significantly associated with PsA susceptibility (p=0.0136) and severity of clinical and laboratory parameters (p values ranging from 0.016 to 2.908 x 10-12). The difference in severity was accounted for by the difference between the AA and GA genotypes with respect to the GG genotype. These findings suggest that TNF-α gene polymorphisms may influence PsA susceptibility and severity. Psoriatics arthritis (PsA) is a complex immunemediated disease that results from the interplay between multiple genetic and environmental factor [1]. Although the pathogenesis of PsA remains elusive, there is evidence that genetic factors may contribute to the etiology of the disease [2]. Is has been estimated that at least one third of the genetic contribution to PsA resides in the major histocompatibility complex (MHC) region [2]. The tumor necrosis factor (TNF)-α gene, which is located in the short arm of chromosome 6 in the MHC class III region between the HLA-B and HLA-DR genes, has been proposed as a major candidate gene in PsA [3]. This hypothesis is supported by studies which have found high serum, synovial fluid and synovial membrane TNF-α levels in patients with PsA [4,5]. Several single nucleotide polymorphisms (PNPs) have been identified in the TNF-α gene promoter [6]. In particular, two common polymorphisms, namely G to A substitutions at positions -238 and -308 have been studied in patients with PsA. However, association studies of these two TNF-α polymorphisms and genetic susceptibility to PsA have lead to conflicting results [7-12]. Previous studies have indicated the potential role of the SNP at +489 position in the first intron of the TNF-α gene in the susceptibility to some rheumatic autoimmune diseases like rheumatoid arthritis [13], systemic lupus erythematosus [14] and systemic sclerosis [15]. However, to our present knowledge, studies on the association of +489 polymorphism with PsA susceptibility and response to TNF-α inhibitors are not reported in the literature. Is this study we investigated the role of SNPs at +489 within the TNF-α gene in PsA susceptibility and severity.

scholarly journals Associations between tumor necrosis factor-α and lymphotoxin-α polymorphisms and idiopathic recurrent miscarriage

Reproduction ◽  
2008 ◽  
Vol 135 (3) ◽  
pp. 397-403 ◽  
Author(s):  
W Zammiti ◽  
N Mtiraoui ◽  
H Khairi ◽  
J-C Gris ◽  
W Y Almawi ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Recurrent Miscarriage ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Tnf Α ◽  
Idiopathic Recurrent Miscarriage ◽  
Factor Α ◽  
Lymphotoxin Α ◽  
Necrosis Factor

Heightened expression of tumor necrosis factor (TNF)-α and lymphotoxin-α (LT-α) was associated with pregnancy complications, including idiopathic recurrent miscarriage (RM). Whereas TNF-α and LT-α gene polymorphisms affect serum cytokine concentrations, their contribution to RM is controversial. The single nucleotide polymorphisms (SNPs) TNF-α (−238G/A, −308G/A) and LT-α (+252A/G) were investigated in 350 RM women and 200 control women. Higher frequency of the TNF-α −238A, but not the TNF-α −308A or the LT-α+252G, allele was seen in patients, with comparable frequencies of TNF-α −238G/A, TNF-α −308G/A, and LT-α+252A/G genotypes seen between both groups, except for TNF-α −238G/G, which was lower in patients. Regression analysis confirmed the association of the TNF-α −238G/A SNP with idiopathic RM, and both TNF-α −308A/TNF −238G/LT-α+252Gand TNF-α −308G/TNF-α −238A/LT-α+252Ghaplotypes played a susceptible role in idiopathic RM. TNF-α −238G/A and −238A/A, and LT-α+252G/G genotypes were positively associated only with exclusively early RM. This supports the concept of the association of TNF-α (−238G/A) and LT-α (+252A/G) polymorphic variants in idiopathic RM.

scholarly journals Tumor Necrosis Factor Alpha-863 C/A Single Nucleotide Polymorphisms and Nephrotic Syndrome

2020 ◽  
Vol 10 (03) ◽  
pp. 319-322
Author(s):  
Ahmed Abdul-Hassan Abbas ◽  
Zainab J. Fadhil ◽  
Shatha Hussein Ali
Keyword(s):  
Nephrotic Syndrome ◽  
Tumor Necrosis Factor ◽  
Serum Level ◽  
Tumor Necrosis ◽  
Nucleotide Polymorphisms ◽  
Necrosis Factor Alpha ◽  
Single Nucleotide ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

Introduction: Cytokines act as a mediator of inflammation in childhood nephrotic syndrome. Polymorphisms of cytokines genes may influence susceptibility to nephrotic syndrome (NS), as well as, patients’ steroid responses. Objective: To study the association of tumor necrosis factor-alpha single nucleotide polymorphisms (TNF-α SNP) (-863 C/A) with the development of NS in addition to access to their effects on serum level of TNF and the response to steroid therapy. Patients and Methods: This study included 60 patients (19 female and 41 male) with nephrotic syndrome; their ages ranged from 2 to 18 years. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to assess the TNF-α gene polymorphism. Results: According to the digestion pattern of RFLP-PCR products of TNF-α-863, this polymorphism had three genotypes, which were CC, CA, and AA, in both NS patients and controls. Also, the current result observed that -863 SNP do not affect the serum level of TNF-α and steroid responsiveness in patients with nephrotic syndrome. Conclusion: This polymorphism did not show any significant association with response to steroid therapy and TNF serum level neither at genotype nor at allele level.

Single Nucleotide Polymorphisms in Tumor Necrosis Factor-α and Susceptibility to HIV Infection in Local Population of Lahore Pakistan

2020 ◽  
pp. 41-47
Keyword(s):  
Tumor Necrosis Factor ◽  
Hiv Infection ◽  
Promoter Region ◽  
Tumor Necrosis ◽  
Local Population ◽  
Nucleotide Polymorphisms ◽  
Chi Square ◽  
Single Nucleotide ◽  
Tnf Α ◽  
Necrosis Factor

A single nucleotide polymorphism (SNP) is observed at -308 position of the promoter region of tumor necrosis factor (TNF- α) gene due to which TNF is categorized into TNF1 and TNF2 allele. TNF2 allele is associated with higher concentration of TNF- α which in turn is associated with HIV infection. In order to know the association between TNF2 and HIV infection n =75 HIV positive samples and n=15 HIV negative samples were observed for TNF polymorphism. It was found that among the infected patients 53 patients had TNF2.The total percentage of the patients and controls having TNF2 allele was found to be 63.34.%. Chi square value was significant showing that there is a strong correlation between HIV susceptibility and TNF SNPs (-308) of the promoter region.

Abstract 291: Association of Single Nucleotide Polymorphisms in Inflammatory Candidate Genes with Circulating Inflammatory Biomarker Concentrations: The Framingham Heart Study

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Renate Schnabel ◽  
Kathryn L Lunetta ◽  
Martin G Larson ◽  
Josée Dupuis ◽  
John F Keaney ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Single Nucleotide Polymorphisms ◽  
Tumor Necrosis ◽  
Intercellular Adhesion Molecule ◽  
Candidate Gene Approach ◽  
Nucleotide Polymorphisms ◽  
Q Value ◽  
Single Nucleotide ◽  
Inflammatory Biomarker ◽  
Necrosis Factor

Background : Chronic subclinical inflammation is a prominent feature of atherosclerotic disease. The genetic background for this pro-inflammatory state is not well-established. Circulating biomarker concentrations have become attractive candidates to measure disease activity and prognosis. Methods : We examined 2356 single-nucleotide polymorphisms (SNPs) in 235 inflammatory pathway genes in association with 11 circulating inflammatory biomarkers in about 1800 Framingham Offspring cohort participants [CD40 ligand, CRP, intercellular adhesion molecule-1, interleukin-6 (IL6), urinary isoprostanes, monocyte chemoattractant protein-1 (MCP1), myeloperoxidase, P-selectin, tumor necrosis factor alpha, tumor necrosis factor receptor-2, fibrinogen]. We created residuals of log transformed biomarker concentrations adjusting for 16 potential confounders. Only SNPs with call rate ≥0.98 and HWE p>0.01, which had at least 5 minor allele carriers entered analyses. False discovery rate (FDR) and q-value methods were applied. Results : We observed similar results with FDR and q-value methods. A total of 45 associations were significant at a cutoff q value of 0.25. The top SNPs were observed in the SELP gene in association with P-selectin concentrations (rs6136 [nonsynonymous], p= 5.17*10 −39 , rs3753305 [intronic], p= 6.17*10 −9 ) and the ICAM1 gene in relation to ICAM-1 concentrations (rs1799969 [coding-nonsynonymous], p= 1.32*10 −8 ). Lowest p-values for trans-acting SNPs were observed for APCS (rs1374486 [function unknown], p= 1.01*10 −7 , and rs6695377 [function unknown], p= 1.85*10 −7 ) with MCP-1 concentrations and for IL6R (rs8192284 [coding-nonsynonimous,intronic], p= 3.36*10 −5 ) with IL6 concentrations. In addition, we could replicate reported findings for rs1799969, and rs5498 in the ICAM-1 gene in relation to ICAM-1 concentrations as well as associations of SNPs rs2857654, rs1024611, and rs2857657 in the CCL-2 gene with MCP-1 concentrations. Conclusions : The results of this candidate gene approach support the relevance of genetic variation for circulating inflammatory biomarker traits. Some former findings were confirmed and novel potential candidates are reported. Our findings merit replication in other cohorts.

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