Effects of a Tumour Necrosis Factor (TNFα) Promoter Base Transition on Trancriptional Activity

Wilson, Anthony G.; Symons, J. A.; McDowell, Tarra L.; Giovine, F. S. Di; Duff, G. W.

doi:10.1042/cs045031pa_pt2

Cited by 43 publications

(65 citation statements)

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“…This association appears to be inconsistent with the finding of previous studies 10,11 that TNFB2 and TNFA2 but not TNFA1 were associated with increased TNF-␣ production. In fact, our data demonstrate no association of either TNFA2 or TNFB2 with increased levels of proinflammatory cytokines in patients with CHF.…”

Section: Discussioncontrasting

confidence: 56%

Effects of Tumor Necrosis Factor Gene Polymorphisms on Patients With Congestive Heart Failure

et al. 1998

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Background-Tumor necrosis factor-␣ (TNF-␣) is known to be elevated in patients with congestive heart failure (CHF).Two biallelic polymorphisms have been identified in the TNF gene locus: one in the promoter region of TNF-␣ (TNFA1/2), and the other in the first intron of TNF-␤ (TNFB1/2). Both TNFA2 and TNFB2 alleles are associated with high TNF-␣ production in vitro and susceptibility to inflammatory diseases. Given the importance of TNF-␣ in the pathogenesis of CHF, we studied the prevalence of TNF gene polymorphisms in CHF patients and the correlation of genotypes to in vivo TNF-␣ levels. Methods and Results-TNFA and TNFB genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism technique. There were no differences in the TNF allele frequencies between CHF (nϭ229; TNFA1/2ϭ0.84/0.16, TNFB1/2ϭ0.33/0.67) and control subjects (nϭ139; TNFA1/2ϭ0.84/0.16, TNFB1/2ϭ0.32/0.68). In 211 patients with CHF, circulating levels of TNF-␣ and the soluble receptors type I and type II were measured by ELISA: 6.18Ϯ3.59 pg/mL, 1768Ϯ761 pg/mL, and 4484Ϯ1750 pg/mL, respectively. There were no correlations between TNFA or TNFB genotypes and circulating levels of TNF-␣ or its soluble receptors in the CHF patients. Conclusions-Despite their association with other inflammatory diseases, neither TNFA nor TNFB polymorphisms are related to the presence of CHF or the elevation of circulating TNF-␣. Thus, other factors may be more important in determining the circulating levels of

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Section: Discussioncontrasting

confidence: 56%

Effects of Tumor Necrosis Factor Gene Polymorphisms on Patients With Congestive Heart Failure

et al. 1998

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“…However, its location within a consensus sequence for the transcription factor AP-2 in the promoter region of the gene 11 and the association of this variant with higher constitutive and inducible levels of TNF-a gene transcription in adipose tissue 21 suggests that this variant could play a role in the development of obesity and related phenotypes. 4 Interestingly, obesity is known to be associated with increased levels of TNF-a mRNA and protein in fat tissue both in humans 5 and in genetically obese or diabetic rodents.…”

Section: Discussionmentioning

confidence: 99%

Tumor necrosis factor-α−308 G/A polymorphism in obese Caucasians

et al. 2001

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OBJECTIVE: Tumor necrosis factor-a (TNF-a) is expressed primarily in adipocytes, and elevated levels of this cytokine have been linked to obesity and insulin resistance. Recently, the A allele of a polymorphism in the 5H -¯anking region of the TNF-a gene (G7308A) has been reported to be more frequent in obese than in lean subjects and has also been associated with increased expression of this cytokine in fat tissue and in¯uences fat mass and insulin resistance. We, therefore, examined the relationship between this variant and obesity in a German Caucasian population. SUBJECTS AND METHODS:We genotyped 176 index subjects recruited within the framework of the BErG (Berlin Erna Èhrung Geschwister)-Study for the TNF-a-G7308A polymorphism. Subjects were characterized for weight, height, waist and hip circumference, body mass index (BMI), body composition, glucose tolerance, leptin and angiotensinogen levels. RESULTS: The frequency of the 7308A allele (0.18) was similar to that reported previously and genotype distribution was in Hardy ± Weinberg equilibrium (GG, n 118; GA, n 53; AA, n 5). There was a signi®cant difference in allele frequencies of the polymorphism by BMI quartiles (I,`27.3 kgam 2 ; II, 27.3 ± 31.9 kgam 2 ; III, 31.9 ± 36.5 kgam 2 ; IV, b 36.5 kgam 2 , in each quartile n 44) with 7308A allele carriers having a higher BMI than G allele carriers (P 0.013). Despite previous smaller studies that have related insulin resistance to the G7308A polymorphism, we found no relationship between glucose and insulin response during an oral glucose tolerance test (OGTT) and the polymorphism. Furthermore, none of the plasma parameters were related to the polymorphism. CONCLUSION: Our ®ndings support the hypothesis that the G7308A polymophism of the TNF-a gene is associated with BMI. The G7308A polymorphism may, therefore, represent a genetic marker for increased susceptibility for obesity in Caucasians.

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“…17 Besides, the A À308 allele may inhibit repressors of transcription. 18 The TNF a promoter polymorphism may also be functionally silent or have selectable effects only when there is linkage with selectable HLA alleles. 18,19 The presence of a G to A polymorphism at position 308 of the TNF a promoter gene could increase transcription six-to seven-fold.…”

Section: Discussionmentioning

confidence: 99%

“…18 The TNF a promoter polymorphism may also be functionally silent or have selectable effects only when there is linkage with selectable HLA alleles. 18,19 The presence of a G to A polymorphism at position 308 of the TNF a promoter gene could increase transcription six-to seven-fold. 20 It is obvious that the variable polymorphisms that lie within the promoter region of the TNF a locus make it a likely candidate for playing a regulatory role in disease.…”

Section: Discussionmentioning

confidence: 99%

Association of tumour necrosis factor alpha −308 gene polymorphism with primary open-angle glaucoma in Chinese

Lin

Tsai

Chen

et al. 2003

Eye

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Purpose Genetic factors are known to play a role in the aetiology of glaucoma, and in particular the role of the immune system is highly suspected. In this study, we evaluated the association between tumour necrosis factor alpha À308 (TNF a À308) and primary open-angle glaucoma (POAG). Methods A total of sixty POAG patients and 103 healthy volunteers as control group were enrolled in this case-controlled study. Furthermore, we used polymerase chain reaction based analysis to resolve the TNF a À308 polymorphism. Statistical analysis for the relative risk of TNF a À308 polymorphism was compared by the v 2 test.Results There were significant differences in the distribution of the polymorphism between the POAG patients and the control subjects (P ¼ 0.00016; Po0.05) and it was found that the A À308 allele occurred more frequently in POAG patients (odds ratio: 2.72; 95% confidence interval: 1.66-4.45).Conclusion The results of our study concluded that the distribution of TNF a À308 was significantly higher in the POAG patients than in the control group. Therefore, the A À308 allele appears to be associated with POAG and, therefore, could be used as a genetic marker for disease mapping. POAG is a complex disease, and a single gene could not be responsible. Understanding the role of genetic polymorphisms, like TNF a, could be a prediction of the disease and useful for developing new treatments for POAG.

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Effects of a Tumour Necrosis Factor (TNFα) Promoter Base Transition on Trancriptional Activity

Cited by 43 publications

References 0 publications

Effects of Tumor Necrosis Factor Gene Polymorphisms on Patients With Congestive Heart Failure

Effects of Tumor Necrosis Factor Gene Polymorphisms on Patients With Congestive Heart Failure

Tumor necrosis factor-α−308 G/A polymorphism in obese Caucasians

Association of tumour necrosis factor alpha −308 gene polymorphism with primary open-angle glaucoma in Chinese

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