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Tumor necrosis factor-alpha gene polymorphisms and susceptibility to ischemic heart disease: A systematic review and meta-analysis.

ABSTRACT: A number of studies had reported the association between tumor necrosis factor-alpha (TNF-?) gene polymorphisms and ischemic heart disease (IHD) risk. However, the results remained controversial. Therefore, we performed a systematic review with multiple meta-analyses to provide the more precise estimations of the relationship.We systematically searched electronic databases (PubMed, the Web of Science, EMBASE, Medline, Chinese National Knowledge Infrastructure, WanFang and ChongQing VIP Database) for relevant studies published up to February 2017. The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for assessing the association. The present meta-analysis was performed using STATA 12.0 software.In total, 45 articles with 17,375 cases and 15,375 controls involved were included. Pooled ORs revealed a significant association between TNF-? -308G/A gene polymorphism and IHD (A vs. G: OR?=?1.22, 95% CI?=?1.10-1.35; (AA?+?GA) vs. GG: OR?=?1.18, 95% CI?=?1.03-1.36; (AA vs. (GA+GG): OR?=?1.37, 95% CI?=?1.08-1.75)), indicating that the TNF-? -308A allele might be an important risk factor for IHD. No association between other TNF-? gene polymorphisms and susceptibility to IHD were observed. No publication bias were found. Sensitivity analyses indicated that our results were stable.The present study indicated a possible association between the TNF-? -308G/A gene polymorphism and IHD risk. However, evidence was limited to confirm the role of TNF-? -238G/A, -857C/T, -863C/A, -1031T/C and other TNF-? gene polymorphisms in the risk of IHD.

SUBMITTER: Zhang P

PROVIDER: S-EPMC5411221 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Tumor necrosis factor-alpha gene polymorphisms and susceptibility to ischemic heart disease: A systematic review and meta-analysis.

Zhang Peng P Wu Xiaomei X Li Guangxiao G He Qiao Q Dai Huixu H Ai Cong C Shi Jingpu J

Medicine 20170401 14

<h4>Background</h4>A number of studies had reported the association between tumor necrosis factor-alpha (TNF-α) gene polymorphisms and ischemic heart disease (IHD) risk. However, the results remained controversial. Therefore, we performed a systematic review with multiple meta-analyses to provide the more precise estimations of the relationship.<h4>Methods</h4>We systematically searched electronic databases (PubMed, the Web of Science, EMBASE, Medline, Chinese National Knowledge Infrastructure, ...[more]

PMID: 28383437

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Project description:BackgroundTumor necrosis factor-α (TNF-α) may play an important role in the recalcitrant inflammatory and hyperproliferative dermatosis of psoriasis, and there may be a relationship between TNF-α polymorphisms and psoriasis risk.MethodsWe performed a meta-analysis to evaluate the associations between TNF-α polymorphisms and psoriasis. Electronic searches of Pubmed, Embase, and Web of Science were performed for all publications on the associations between TNF-α polymorphisms and psoriasis through September 26, 2012. The pooled odds ratios (ORs) with their 95% confidence interval (95%CIs) were calculated to assess the associations.ResultsSixteen case-control studies with a total of 2,253 psoriasis cases and 1,947 controls on TNF-α 308 G/A polymorphism and fourteen studies on TNF-α 238 G/A polymorphism with 2,104 cases and 1,838 controls were finally included into the meta-analysis. Overall, TNF-α 308 G/A polymorphism was significantly associated with decreased risk of psoriasis under three genetic comparison models (for A versus G: fixed-effects OR 0.71, 95%CI 0.62-0.82, P < 0.001; for AG versus GG: fixed-effects OR 0.67, 95%CI 0.57-0.78, P < 0.001; for AA/AG versus GG: fixed-effects OR 0.67, 95%CI 0.58-0.78, P < 0.001). In addition, TNF-α 238 G/A polymorphism was associated with increased risk of psoriasis under three genetic models (for A versus G: fixed-effects OR 2.46, 95%CI 2.04-2.96, P < 0.001; for AG versus GG: fixed-effects OR 2.69, 95%CI 2.20-3.28, P < 0.001; for AA/AG versus GG: fixed-effects OR 2.68, 95%CI 2.20-3.26, P < 0.001). Subgroup analysis by ethnicity identified a significant association between TNF-α 308 G/A polymorphism and decreased risk of psoriasis in both Caucasians and Asians and a significant association between TNF-α 238 G/A polymorphism and increased risk of psoriasis in Caucasians.ConclusionsThe meta-analysis suggests that TNF-α 308 G/A polymorphism is associated with decreased risk of psoriasis, while TNF-α 238 G/A is associated with increased risk of psoriasis.

Project description:PurposeThis meta-analysis was performed to clarify the association between tumor necrosis factor alpha (TNF-α) gene polymorphisms and open angle glaucoma (OAG) risks, and the association between the TNF-α level in aqueous humor (AH) and the risks of glaucoma.MethodsA computerized literature search was performed for the relevant available studies from three databases including PubMed, ISI Web of Science, and Embase. The fixed or random effect model was selected based on the heterogeneity test using the Q test and the I(2) statistic. The associations between TNF-α gene polymorphisms and OAG risks were estimated by calculating pooled odds ratios (ORs) and the 95% confidence interval (CI), while a pooled standardized mean difference with 95% CI was used for the comparison of TNF-α levels in AH between patients with OAG and controls. Publication bias was estimated using Begg's funnel plots and Egger's regression test.ResultsA total of 14 (1,182 cases and 3,003 controls), five (808 cases and 1,039 controls), three (645 cases and 666 controls), and three studies (404 cases and 625 controls) were finally included in the analyses for the associations between TNF-α -308G/A, -857C/T, -863C/A, and -238G/A polymorphisms and the risks of OAG, respectively. The combined results showed that the TNF-α -308G/A gene polymorphism was significantly associated with risks of high-tension glaucoma (A versus G: OR=1.660, 95% CI=1.033-2.667; AA/AG versus GG: OR=1.713, 95% CI=1.10-2.651), but not with normal tension glaucoma or exfoliation glaucoma. Ethnicity-stratified analysis revealed that a significant association also existed in Asians (A versus G: OR=1.947, 95% CI=1.097-3.456; AA/AG versus GG: OR=1.949, 95% CI=1.140-3.332). None of the other polymorphisms was significantly associated with OAG risks. Furthermore, the pooled results of six studies showed that the TNF-α levels in the AH of patients with OAG was higher than that of the control subjects (standardized mean difference=0.517, 95% CI=0.207-0.826, p=0.001). Probability of publication bias was low across all comparisons illustrated by the funnel plots and Egger's test.ConclusionsThis meta-analysis suggests that patients with OAG may have higher TNF-α levels compared with the control subjects, and the TNF-α -308G/A polymorphism is significantly associated with the risks of high-tension glaucoma. Since potential confounders could not be ruled out completely, further studies are needed to confirm these results.

Project description:Tumor Necrosis Factor (TNF)-α, is a paracrine inhibitor of melanocytes, which plays a critical role in the pathogenesis of several autoimmune diseases including vitiligo, as abnormal immune responses have frequently been observed in vitiligo patients. Moreover, vitiligo patients show higher lesion levels of TNF-α. Genetic polymorphisms in the promoter region of TNF-α are involved in the regulation of its expression. The present study explores TNF-α promoter polymorphisms and correlates them with TNF-α transcript and protein levels in vitiligo patients and controls of Gujarat along with its effect on disease onset and progression. PCR-RFLP technique was used for genotyping of these polymorphisms in 977 vitiligo patients and 990 controls. TNF-α transcript and protein levels were measured by Real time PCR and ELISA respectively. The genotype and allele frequencies for the investigated polymorphisms were significantly associated with vitiligo patients. The study revealed significant increase in TNF-α transcript and protein levels in vitiligo patients compared to controls. In particular, haplotypes: AATCC, AACCT, AGTCT, GATCT, GATCC and AGCCT were found to increase the TNF-α levels in vitiligo patients. Analysis of TNF-α levels based on the gender and disease progression suggests that female patients and patients with active vitiligo had higher levels of TNF-α. Also, the TNF-α levels were high in patients with generalized vitiligo as compared to localized vitiligo. Age of onset analysis of the disease suggests that the haplotypes: AACAT, AACCT, AATCC and AATCT had a profound effect in the early onset of the disease. Moreover, the analysis suggests that female patients had an early onset of vitiligo. Overall, our results suggest that TNF-α promoter polymorphisms may be genetic risk factors for susceptibility and progression of the disease. The up-regulation of TNF-α transcript and protein levels in individuals with susceptible haplotypes advocates the crucial role of TNF-α in autoimmune pathogenesis of vitiligo.

Project description:BackgroundInflammation is one of the factors associated with prostate cancer. The cytokine tumor necrosis factor-alpha (TNF-α) plays an important role in inflammation. Several studies have focused on the association between TNF-α polymorphisms and prostate cancer development. Our meta-analysis aimed to estimate the association between TNF-α rs1800629 (- 308 G/A), rs361525 (- 238 G/A) and rs1799724 polymorphisms and prostate cancer risk.MethodsEligible studies were identified from electronic databases (PubMed, Embase, Wanfang and CNKI) using keywords: TNF-α, polymorphism, prostate cancer, until Nov 15, 2019. Odds ratios (ORs) with 95% confidence intervals (CIs) were applied to determine the association from a quantitative point-of-view. Publication bias and sensitivity analysis were also applied to evaluate the power of current study. All statistical analyses were done with Stata 11.0 software.ResultsTwenty-two different articles were included (22 studies about rs1800629; 8 studies for rs361525 and 5 studies related to rs1799724). Overall, no significant association was found between rs1800629 and rs1799724 polymorphisms and the risk of prostate cancer in the whole (such as: OR = 1.03, 95% CI = 0.92-1.16, P = 0.580 in the allele for rs1800629; OR = 0.95, 95% CI = 0.84-1.07, P = 0.381 in the allele for rs1799724). The rs361525 polymorphism also had no association with prostate cancer in the cases (OR = 0.93, 95% CI = 0.66-1.32, P = 0.684 in the allele) and ethnicity subgroup. The stratified subgroup of genotype method, however, revealed that the rs361525 variant significantly decreased the risk of prostate cancer in the Others (OR = 0.65, 95% CI = 0.47-0.89, P = 0.008, A-allele vs G-allele) and PCR-RFLP (OR = 2.68, 95% CI = 1.00-7.20, P = 0.050, AG vs GG or AA+AG vs GG) methods.ConclusionsIn summary, the findings of the current meta-analysis indicate that the TNF-α rs1800629, rs361525 and rs1799724 polymorphisms are not correlated with prostate cancer development, although there were some pooled positive results. Further well-designed studies are necessary to form more precise conclusions.

Dataset Information

Tumor necrosis factor-alpha gene polymorphisms and susceptibility to ischemic heart disease: A systematic review and meta-analysis.

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Tumor necrosis factor-alpha gene polymorphisms and susceptibility to ischemic heart disease: A systematic review and meta-analysis.

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