Tumor necrosis factor-α –308G/A gene polymorphism in Egyptian children with immune thrombocytopenic purpura

Sissy, Maha Hamdi El; Sissy, A.H. El; Elanwary, Sherif

doi:10.1097/mbc.0000000000000089

Cited by 15 publications

(11 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The polymorphic A allele frequency was significantly higher in ITP patients than in the controls, conferring almost two-fold increased ITP risk [27]. However, similar to our results, both the frequency of TNF-a (-308) G/A and A/ A as well as A allele frequency were not significantly different in newly diagnosed than chronic patients with ITP.…”

Section: Discussionsupporting

confidence: 67%

“…Saitoh et al [14] found no significant relationship between IL-17F 7488TT/TC and treatment response, including CR, R, and corticosteroid dependence as well as the study of El Sissy et al [27] who found no difference in treatment response for those harboring TNF-a (-308) polymorphic genotype between the newly diagnosed and chronic patients with ITP.…”

Section: Discussionmentioning

confidence: 96%

“…The previous Egyptian study [27] reported that the frequency of TNF-a (-308) G/A polymorphic genotype was significantly lower in males. Otherwise, there was no statistically significant difference noticed between the newly diagnosed and chronic patients with regard to the degree of thrombocytopenia, bleeding or splenomegaly.…”

Section: Discussionmentioning

confidence: 97%

See 2 more Smart Citations

Cytokine gene polymorphism [tumor necrosis factor-alpha (–308), IL-10 (–1082), IL-6 (–174), IL-17F, 1RaVNTR] in pediatric patients with primary immune thrombocytopenia and response to different treatment modalities

Mokhtar

El-Beblawy

Adly

et al. 2016

Blood Coagulation &Amp; Fibrinolysis

View full text Add to dashboard Cite

To evaluate the association between development, progression, and response to therapy among patients with immune thrombocytopenia (ITP) and different cytokine gene polymorphisms known to be related to autoimmunity [tumor necrosis factor (TNF)-alpha, interleukin (IL)-10, IL-6, IL-17, IL-1Ra]. A total of 50 pediatric patients with ITP (20 newly diagnosed, 30 chronic) and 50 healthy controls were investigated via PCR-restriction fragment length polymorphism analysis for cytokine gene polymorphism. Compared with controls, all patients showed a higher frequency of IL-6-174 CC [P = 0.0001, odds ratio (OR) = 7.048, 95% confidence interval (CI) = 2.18-22.7], higher GA genotype of TNF-α (-308) (P = 0.001, OR = 6.469, 95% CI = 2.0-20.9), higher CC genotype of IL-17F (P = 0.0001, OR = 55.545, 95% CI = 14.4-213.2), higher GG of IL-10-1082 (P = 0.029, OR = 3.6, 95% CI = 1.08-12.18), and A1A2 genotype of IL-1Ra (P = 0.039, OR = 2.374, 95% CI = 1.03-5.4). IL-10 GA and IL-1Ra A1A1 genotypes were higher among chronic patients (P = 0.042, P = 0.001 respectively) compared with newly diagnosed ones. Best platelet response to steroid treatment was found among GC genotype of IL-6 (-174) and GG genotype of IL-10 (-1082) in all patients with ITP. This suggests that previously mentioned cytokine gene polymorphisms possibly contribute to the susceptibility of acquisition of childhood ITP. Furthermore, GA genotype of IL-10 and A1A1 genotype of IL-1Ra polymorphisms are associated with increased risk of chronic ITP. IL-6 (-174) and IL-10 (-1082) genes might play a role in the effectiveness of steroid therapy among patients with ITP.

show abstract

Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 96%

See 1 more Smart Citation

Cytokine gene polymorphism [tumor necrosis factor-alpha (–308), IL-10 (–1082), IL-6 (–174), IL-17F, 1RaVNTR] in pediatric patients with primary immune thrombocytopenia and response to different treatment modalities

Mokhtar

El-Beblawy

Adly

et al. 2016

Blood Coagulation &Amp; Fibrinolysis

View full text Add to dashboard Cite

show abstract

“…Higher levels of TNF have been reported in the plasma/serum from ITP patients,(Culic et al , 2013; Jernas et al , 2013; Talaat et al , 2014) although TNF expression levels in specific ITP cell types, such as CD4+ T lymphocytes, has not been examined. Interestingly, ITP patients have an increased frequency of TNF −308 A polymorphic allele associated with higher TNF-α production (Pehlivan et al , 2011; Sarpatwari et al , 2011; El Sissy et al , 2014). TNF binds to two distinct receptors: TNFRSF1A (TNFRI, p55) and TNFRSF1B (TNFRII; p75) (Locksley et al , 2001).…”

mentioning

confidence: 99%

In vitro TNF blockade enhances ex vivo expansion of regulatory T cells in patients with immune thrombocytopenia

2014

View full text Add to dashboard Cite

Summary Tumour necrosis factor-α (TNF) is an inflammatory cytokine that is elevated in a number of autoimmune diseases including immune thrombocytopenia (ITP), a bleeding disorder characterized by low platelet counts. In vitro TNF blockade increases expansion of the regulatory T cell (Treg) IKZF2 (also termed Helios) subset in T cell-monocyte cocultures from healthy donors, but its role on proliferative responses of Tregs in ITP patients, who have altered immunoregulatory compartment, remains unclear. TNF in CD4+ T cells from patients with chronic ITP were elevated and negatively correlated with peripheral Treg frequencies, suggesting a possible inhibitory effect of TNF on ITP Tregs. In vitro antibody neutralization with anti-TNF in T cell-monocyte cocultures resulted in a robust expansion of pre-existing ITP Tregs, higher than in healthy controls. Similar to the effects of anti-TNF antibodies, TNF blockade with antibodies against TNFRSF1B (anti-TNFRSF1B, previously termed anti-TNFRII) almost doubled ITP Treg expansion whereas neutralization with anti-TNFRSF1A (anti-TNFRI) antibodies had no effect on proliferative responses of Tregs. In addition, TNFRSF1B levels on ITP Tregs were significantly elevated, which may explain the increased susceptibility of patient Tregs to the actions of TNF blockade. Altogether, these data raise the possibility that TNF blockers, through their ability to increase Treg proliferation, may be efficacious in ITP patients.

show abstract

“…It is also important to note that the presence of H. pylori increases TNF-α expression, a process which reflects the interaction between this inflammatory mediator and gastric carcinogenesis [8]. Polymorphisms that increase TNF-α expression have now been associated with autoimmune diseases and cancer [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Influence of functional polymorphisms in TNF-α, IL-8, and IL-10 cytokine genes on mRNA expression levels and risk of gastric cancer

et al. 2015

View full text Add to dashboard Cite

Functional polymorphisms in promoter regions can produce changes in the affinity of transcription factors, thus altering the messenger ribonucleic acid (mRNA) expression levels of inflammatory cytokines associated with the risk of cancer development. The goal of this study was to evaluate the influence that polymorphisms in the cytokine genes known as TNF-α-308 G/A (rs1800629), TNF-α-857 C/T (rs1799724), IL-8-251 T/A (rs4073), IL-8-845 T/C (rs2227532), and IL-10-592 C/A (rs1800872) have on changes to mRNA expression levels and on the risks of chronic gastritis (CG) and gastric cancer (GC). A sample of 723 individuals was genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Relative mRNA expression levels were measured using quantitative real-time PCR (qPCR). Polymorphisms TNF-α-308 G/A and IL-8-251 A/T were not associated with risks of these gastric lesions. However, TNF-α-857 C/T, IL-8-845 T/C, and IL-10-592 C/A were found to be associated with a higher risk of GC, and IL-10-592 C/A was found to be associated with a higher risk of CG. The relative mRNA expression levels (RQ) of TNF-α, IL-8, and IL-10 were markedly downregulated in the CG group (median RQs = 0.128, 0.247, and 0.614, respectively), while the RQ levels of TNF-α in the GC group were upregulated (RQ = 2.749), but were basal for IL-8 (RQ = 1.053) and downregulated for IL-10 (RQ = 0.179). When the groups were stratified according to wild-type and polymorphic alleles, only for IL-8-845 T/C the polymorphic allele was found to influence the expression levels of this cytokine. IL-8-845 C allele carriers were significantly upregulated in both groups (GC and CG; RQ = 3.138 and 2.181, respectively) when compared to TT homozygotes (RQ = -0.407 and 0.165, respectively). In silico analysis in the IL-8 promoter region revealed that the presence of the variant C allele in position -845 is responsible for the presence of the binding sites for two transcription factors (REL and CREB1), which are involved in increased gene expression. Polymorphic alleles were not shown to have any effect on the expression levels of TNF-α and IL-10. Taken together, our findings provide evidence for an association of TNF-α-857 C/T, IL-8-845 T/C, and IL-10-592 C/A with a higher risk of gastric cancer and also demonstrate the influence that the polymorphic C allele of IL-8-845 has on changes to the gene expression levels of this cytokine.

show abstract

Tumor necrosis factor-α –308G/A gene polymorphism in Egyptian children with immune thrombocytopenic purpura

Cited by 15 publications

References 35 publications

Cytokine gene polymorphism [tumor necrosis factor-alpha (–308), IL-10 (–1082), IL-6 (–174), IL-17F, 1RaVNTR] in pediatric patients with primary immune thrombocytopenia and response to different treatment modalities

Cytokine gene polymorphism [tumor necrosis factor-alpha (–308), IL-10 (–1082), IL-6 (–174), IL-17F, 1RaVNTR] in pediatric patients with primary immune thrombocytopenia and response to different treatment modalities

In vitro TNF blockade enhances ex vivo expansion of regulatory T cells in patients with immune thrombocytopenia

Influence of functional polymorphisms in TNF-α, IL-8, and IL-10 cytokine genes on mRNA expression levels and risk of gastric cancer

Contact Info

Product

Resources

About