Effects of a polymorphism in the human tumor necrosis factor α promoter on transcriptional activation

Wilson, Anthony G.; Symons, Julian; McDowell, Tarra L.; McDevitt, Hugh O.; Duff, Gordon W.

doi:10.1073/pnas.94.7.3195

Cited by 2,098 publications

(1,501 citation statements)

References 45 publications

Supporting

Mentioning

1,393

Contrasting

Unclassified

Order By: Relevance

“…20 TNF2 is a component of an extended MHC haplotype HLA-A1-B8-DR3-DQ2, which is associated with high TNF-a production. 20 The second possibility is that undefined genetic polymorphisms in linkage disequilibrium with haplotype S01 exist in other regions of the hIL-18 gene including coding exons, and contribute to high bioactivity of IL-18 seen in AOSD.…”

Section: Discussionmentioning

confidence: 99%

Association between adult-onset Still's disease and interleukin-18 gene polymorphisms

et al. 2002

View full text Add to dashboard Cite

Recently, we reported that serum concentration of IL-18 is strikingly high in patients with adult-onset Still's disease (AOSD). The aim of the present study was to screen for genetic polymorphisms in the human IL-18 (hIL-18) gene and to determine the association of polymorphisms with susceptibility to AOSD. We investigated the 6.7 kb region upstream of exon 2 of hIL-18 gene, in which a promoter activity had been reported. Sixteen AOSD patients, 144 rheumatoid arthritis (RA) patients and 92 healthy control individuals were studied. We found seven single nucleotide polymorphisms and a single 9 bp insertion which were frequently present in the AOSD patients. Three haplotypes including a unique combination of these polymorphisms were also determined. Of them, haplotype S01 contained all eight of these polymorphisms. The frequency of individuals carrying a diplotype configuration, ie a combination of two haplotypes, of S01/S01 was significantly higher in the AOSD patients than in the healthy controls (P ¼ 0.00059, Fischer's exact probability test, odds ratio [OR] ¼ 7.81, 95% confidence interval [95% CI] ¼ 2. 48-24.65) and the RA patients (P ¼ 0.015, Fischer's exact probability test, OR ¼ 4.0, 95% CI ¼ 1.39-11.54). We therefore conclude that possession of the diplotype configuration of S01/S01 is a major genetic risk factor for susceptibility to AOSD.

show abstract

Section: Discussionmentioning

confidence: 99%

Association between adult-onset Still's disease and interleukin-18 gene polymorphisms

et al. 2002

View full text Add to dashboard Cite

show abstract

“…It is characterized by a single base pair (SBP) polymorphism at position -308 in the promoter of TNFa [6]. The mutation leading to the allele 2 has been shown to be associated with an enhanced transcription of TNFa [7] as well as increased release of TNFa from blood mononuclear cells [8] or whole blood [9] in response to endotoxin.…”

mentioning

confidence: 99%

Lack of association between adult asthma and the tumour necrosis factor α-308 polymorphism gene

Louis¹,

Leyder²,

Malaise³

et al. 2000

Eur Respir J

View full text Add to dashboard Cite

Lack of association between adult asthma and the tumour necrosis factor a-308 polymorphism gene. R. Louis, E. Leyder, M. Malaise, P. Bartsch, E. Louis. #ERS Journals Ltd 2000. ABSTRACT: Tumour necrosis factor (TNF)a is a cytokine endowed with potent inflammatory properties that may contribute to airway inflammation in asthma. It has previously been shown that the single base pair polymorphism-308 (G to A substitution) in the promoter of TNFa gene results in enhanced cytokine secretion. Whether this polymorphism is associated with the presence of phenotypic expression of asthma is questioned.In this study the relative frequency of TNF1 and TNF2 alleles in a population of adult healthy subjects (n=98) and adult Caucasian asthmatics (n=95) was compared taking into account their disease severity, atopic status and their smoking habit.For the whole group of asthma the genotype frequency for 1/1, 1/2, 2/2 were 67%, 33% and 0%, respectively, and not significantly different from those found in the control group that reached 70%, 28% and 2% respectively (p>0.05). The allele frequencies in asthma were 86% and 14% for TNF1 and TNF2 respectively while the corresponding figures were 85% and 15% in the control group (p>0.05). Furthermore, subdividing asthmatics into severe forced expiratory volume in one second <60% pred), atopic or smoking patients did not show any significant association with this TNFa polymorphism.To conclude the polymorphism -308 in the promoter of the TNFa gene does not confer a susceptibility to develop asthma nor to grade its severity. Eur Respir J 2000; 16: 604±608.

show abstract

“…23 Besides, the A 308 allele may inhibit repressors of transcription. 24 The presence of a G to A polymorphism at position 308 of the TNF-a promoter gene could increase transcription six-to seven-fold. 25 The IL-1b gene is located on chromosome 2, in close linkage with another gene of the IL-1 gene family that encodes for IL-1Ra.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of TNF-α and IL-1β polymorphisms in Taiwan Chinese patients with pterygium

Tsai

Lee

Tseng

et al. 2004

Eye

View full text Add to dashboard Cite

Purpose Pterygium, a complex disease, is associated with ultraviolet radiation, immunoinflammatory process, genetic factors, and virus infection. Ultraviolet radiation induces secretion of proinflammatory cytokines by the ocular surface epithelium, inflammatory cells in the tear fluid, or both. Among these cytokines, tumour necrosis factor (TNF)a and interleukin (IL)-1b activate pterygium body fibroblasts, resulting in a phenotype capable of expressing various proteinases associated with extracellular matrix remodelling, angiogenesis, and fibroblast proliferation, which are important for pterygium formation and recurrence. The genetic factor was proposed to play a role in pterygium formation, but there were few studies to clarify this proposition. For investigating genetic factors, the association between pterygium and TNF-a and IL-1b polymorphisms is evaluated in this study. Methods A total of 128 pterygium patients and 103 volunteers without pterygium were enrolled in this study. Polymerase chain reaction-based analysis was used to resolve the TNF-a-308 promoter, IL-1b-511 promoter, IL-1b exon 5, and IL-1 receptor antagonist (IL-1 Ra) polymorphisms. Results There were no significant differences in the frequency of genotypes and alleles of TNF-a-308 promoter, IL-1b-511 promoter, IL-1b exon 5, and IL-1 Ra polymorphisms between both groups. Conclusions The correlation between pterygium and TNF-a-308 promoter, IL-1b-511 promoter, IL-1b exon 5, and IL-1 Ra polymorphisms does not exist and those polymorphisms are not useful genetic markers for pterygium susceptibility. Further studies on other polymorphisms or haplotypes of TNF-a and IL-1b are necessary.

show abstract

Effects of a polymorphism in the human tumor necrosis factor α promoter on transcriptional activation

Cited by 2,098 publications

References 45 publications

Association between adult-onset Still's disease and interleukin-18 gene polymorphisms

Association between adult-onset Still's disease and interleukin-18 gene polymorphisms

Lack of association between adult asthma and the tumour necrosis factor α-308 polymorphism gene

Evaluation of TNF-α and IL-1β polymorphisms in Taiwan Chinese patients with pterygium

Contact Info

Product

Resources

About