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Tumor necrosis factor-alpha 308G>A polymorphism and risk of rheumatic heart disease: a meta-analysis.

ABSTRACT: Rheumatic heart disease (RHD) remains a serious cardiovascular disorder across the world. Tumor necrosis factor alpha (TNF-?) codifies a potent immunomodulator and pro-inflammatory cytokine that mediates diverse pathological processes. A promoter 308G>A polymorphism in TNF-? has been implicated in RHD risk. However, the results remain controversial. Therefore, to evaluate more precise estimations of the relationship, a meta-analysis was performed. A total of 7 studies including 735 RHD cases and 926 controls were involved in this meta-analysis. Overall, our results revealed that there was a significant association with RHD risk in three genetic models (homozygous model: OR = 3.06, 95%CI = 1.22-10.60, P = 0.020; dominant model, OR = 2.03, 95%CI = 1.01-4.07, P = 0.048; and recessive model, OR = 4.26, 95%CI = 2.41-7.55, P < 0.001). Further ethnic population analysis found a significantly increased risk of RHD among Asians and Europeans. Interestingly, similar results were found among hospital-based studies. Begg's funnel plot and Egger's test did not reveal any publication bias. Taken together, this meta-analysis demonstrates that the TNF-? 308G>A polymorphism is associated with RHD susceptibility, and it contributes to the increased risk of RHD. However, additional well-designed studies with larger samples are warranted to confirm these findings.

SUBMITTER: Zheng RL

PROVIDER: S-EPMC3994435 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Tumor necrosis factor-alpha 308G>A polymorphism and risk of rheumatic heart disease: a meta-analysis.

Zheng Ruo-Long RL Zhang Hua H Jiang Wen-Long WL

Scientific reports 20140422

Rheumatic heart disease (RHD) remains a serious cardiovascular disorder across the world. Tumor necrosis factor alpha (TNF-α) codifies a potent immunomodulator and pro-inflammatory cytokine that mediates diverse pathological processes. A promoter 308G>A polymorphism in TNF-α has been implicated in RHD risk. However, the results remain controversial. Therefore, to evaluate more precise estimations of the relationship, a meta-analysis was performed. A total of 7 studies including 735 RHD cases and ...[more]

PMID: 24751687

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Project description:Although numerous studies have suggested the association between TNF-α-308G/A polymorphism and susceptibility to obstructive sleep apnea (OSA), the results remained controversial and ambiguous. We performed the present meta-analysis to derive a more precise estimation.The PubMed, Embase, Cochrane library, Web of Science, China National Knowledge Infrastructure, Wanfang databases, and Weipu databases (until January 8, 2022) were accessed to retrieve relevant articles. Pooled odds ratios (ORs) with 95% confidence interval (95% CI) were calculated using the STATA statistical software.Totally, fourteen studies involving 2595 cases and 2579 controls were enrolled in this meta-analysis. Pooled results demonstrated significant association between TNF-α-308G/A polymorphism and OSA risk for the overall population(allele model:OR = 1.87 [1.47, 2.38] (n = 14), dominant model: OR = 1.88[1.48, 2.39] (n = 14), recessive model:OR = 2.83 [2.00, 4.00] (n = 11), homozygous model:OR = 3.30 [2.32, 4.68] (n = 11), and heterozygous model:OR = 1.67 [1.36, 2.06] (n = 14); P<0.001, respectively).Subgroup analysis showed that in both Caucasians and Asians, the A allele conferred increased risk to OSA compared to the G allele (Caucasians: OR = 1.40[1.03, 1.90] (n = 5), P = 0.033, Asians: OR = 2.30 [1.62, 3.26] (n = 9), P< 0.001). In subgroup analysis restricted to hospital-based individuals, significant association between TNF-α-308G/A polymorphism and OSA risk was identified under each genetic model. Whereas, in population-based individuals, increased risk of OSA were only found in homozygous model (OR = 2.19[1.23, 3.90] (n = 3), P = 0.008) and recessive model (OR = 1.77 [1.00, 3.13] (n = 3), P = 0.048). There was a substantial between-study heterogeneity (I2 = 69.10%) across studies which was explained by source of control participants (P = 0.036) by meta-regression. The results of leave-one-out meta-analysis and publication bias suggested the reliability and stability of our results.This meta-analysis suggested that TNF-α-308A allele may be a risk factor for the development of OSA. However, large scale,multi-center and well-designed case-control studies are needed in the future.

Project description:ObjectiveTumor necrosis factor alpha (TNF-α) is an important cytokine involved in inflammation, immune response, and other biological processes. The association between polymorphism -308G/A in its promoter and the risk of multiple myeloma (MM) is not clear. Thus, we conducted a meta-analysis to clarify this question.Materials and methodsTwelve eligible studies, which included 2204 MM cases and 3478 controls, were enrolled in our meta-analysis by searching the PubMed, China National Knowledge Infrastructure, Scopus, Web of Science, and Google Scholar databases up to December 2018. The effect of polymorphism -308G/A on MM risk was evaluated by calculating the pooled odds ratio (OR) and the 95% confidence interval (CI). Furthermore, the Q-test and I2 statistical analyses were used to estimate the degree of heterogeneity. Sensitivity analysis was conducted to test the robustness of the meta-analysis results. Publication bias was assessed by Egger’s test and visual inspection of a funnel plot.ResultsIn the dominant model, -308G/A polymorphism was associated with reduced MM risk (OR=0.80, 95% CI: 0.65-0.97), and it also demonstrated a significant protective effect with a pooled OR of 0.82 (95% CI: 0.68-0.99) in the Caucasian subgroup. Because of the limited number of individual studies with AA genotype carriers, only eight studies were included in the recessive model, and no significant difference was observed. Moreover, the meta-analysis of the allele frequency demonstrated that the A allele has a protective effect against MM risk with a pooled OR of 0.83 (95% CI: 0.69-0.99). Sensitivity analysis suggested that the synthesized effect size was not influenced by any individual study. Moreover, the Egger’s test statistical analysis suggested that publication bias was not obvious in the present analysis.ConclusionOverall, the -308G/A polymorphism was associated with reduced MM risk in the dominant model and allele frequency. Further investigation is needed to gain better insight.

Project description:The multifactorial pathogenesis of severe malaria is partly attributed to host genes, such as those encoding cytokines involved in complex inflammatory reactions, namely tumor necrosis factor-alpha (TNF-α). However, the relationship between TNF-α -308G >A gene polymorphism (rs1800629) and the severity of Plasmodium falciparum (P. falciparum) malaria remains unclear, which prompts a meta-analysis to obtain more precise estimates. The present meta-analysis aimed to better understand this correlation and provide insight into its association in populations with different ethnicities. Literature search outcomes included eight eligible articles in which TNF-α -308G >A polymorphism was determined in uncomplicated malaria (UM) and severe malaria (SM) of P. falciparum as represented in the case and control groups. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated in standard homozygous, recessive, dominant, and codominant genetic models. Subgroup analysis was based on ethnicity, i.e., Africans and Asians. The analyses included overall and the modified outcomes; the latter was obtained without the studies that deviated from the Hardy-Weinberg Equilibrium. The significant data also underwent sensitivity treatment but not publication bias tests because the number of studies was less than ten. Interaction tests were applied to differential outcomes between the subgroups. Overall and HWE-compliant analyses showed no significant association between the TNF-α -308G >A polymorphism and susceptibility to P. falciparum SM (ORs = 1.10-1.52, 95%CIs = 0.68-2.79; Pa = 0.24-0.68). Stratification by ethnicity revealed that two significant associations were found only in the Asians favoring SM for dominant (OR = 1.95, 95% CI = 1.06-3.61, Pa = 0.03) and codominant (OR = 1.83, 95% CI = 1.15-2.92, Pa = 0.01) under the random-effects model, but not among the African populations. The two significant Asian associations were improved with a test of interaction with P-value of0.02-0.03. The significant core outcomes were robust. Results of the meta-analysis suggest that TNF-α -308G >A polymorphism might affect the risk of P. falciparum SM, particularly in individuals of Asian descent. This supports ethnicity as one of the dependent factors of the TNF-α -308G >A association with the clinical severity of malaria. Further large and well-designed genetic studies are needed to confirm this conclusion.

Dataset Information

Tumor necrosis factor-alpha 308G>A polymorphism and risk of rheumatic heart disease: a meta-analysis.

Publications

Tumor necrosis factor-alpha 308G>A polymorphism and risk of rheumatic heart disease: a meta-analysis.

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