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Tumor necrosis factor-alpha -308G/A gene polymorphism and novel biomarker profiles in patients with Takayasu arteritis.

ABSTRACT: BACKGROUND:Takayasu arteritis (TA) is an idiopathic chronic inflammatory disease of the aorta and its branches, leading to stenosis, occlusion, and aneurysmal dilatation. Tumor necrosis factor-alpha (TNF-?) is a cytokine with pleomorphic actions and plays a pivotal role in inflammation; the serum level of TNF-? is genetically determined. However, the literature lacks adequate information on the association of TNF-? polymorphisms with TA. Hence, the present study investigates the contribution of TNF-? polymorphism toward the complex etiology of TA. METHODS:A cross-sectional study was performed in 87 patients with TA and 90 controls. A promoter region polymorphism of TNF-?, rs1800629 G/A, or -308G/A was genotyped in all the study subjects followed by a case-control association study. Furthermore, to understand the biomarker profile, levels of specific markers such as erythrocyte sedimentation rate, serum high-sensitivity C-reactive protein, interleukin-18, interleukin-6, and TNF-? were measured in all the study subjects. RESULTS:All the inflammatory markers were significantly higher in the TA patients than in the controls. The genetic study (available for 57 TA patients and 36 controls) revealed that the TNF-? -308A allele was overrepresented in the TA patients (12% vs 7%). The TNF-? -308A allele correlated with the increased TNF-? levels, but it could not attain significance because of a small sample size. CONCLUSION:The TNF-? -308G/A polymorphism is associated with TNF-? levels in Indian population, which might have implications for clinical risk stratification and treatment. The different TNF-? gene promoter polymorphism might contribute to the molecular pathogenesis of TA. However, further study of the underlying mechanism is warranted.

SUBMITTER: Sarkar PG

PROVIDER: S-EPMC6310777 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Tumor necrosis factor-alpha -308G/A gene polymorphism and novel biomarker profiles in patients with Takayasu arteritis.

Sarkar Prattay Guha PG Gupta Mohit Dayal MD Girish M P MP Bansal Ankit A Kohli Samantha S Saijpaul Rajni R Tyagi Sanjay S Pasha Qadar Q

Indian heart journal 20181010

<h4>Background</h4>Takayasu arteritis (TA) is an idiopathic chronic inflammatory disease of the aorta and its branches, leading to stenosis, occlusion, and aneurysmal dilatation. Tumor necrosis factor-alpha (TNF-α) is a cytokine with pleomorphic actions and plays a pivotal role in inflammation; the serum level of TNF-α is genetically determined. However, the literature lacks adequate information on the association of TNF-α polymorphisms with TA. Hence, the present study investigates the contribu ...[more]

PMID: 30595251

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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.

Project description:BackgroundInflammation constitutes one of the important components of colorectal cancer (CRC) pathogenesis. Tumor necrosis factor-α (TNF-α), a cytokine and an important inflammatory mediator plays a pivotal role in the malignant cellular proliferation, angiogenesis, tissue invasion and metastasis in CRC. The studies on association of various polymorphisms in human TNF-α gene including TNF-α-308G/A single nucleotide polymorphism (SNP) are limited, mixed and inconclusive.Materials and methodsThe aim of this study was to analyze the association of TNF-α-308G/A promoter SNP with colorectal cancer (CRC) susceptibility and development risk and also to evaluate the modifying effects of possible TNF-α-308G/A genotypes on different risk factors of CRC in ethnic population of Kashmir, India through a case-control setup. The genotype frequencies of TNF-α-308G/A promoter SNP were compared between 142 CRC patients and 184 individually matched healthy controls by using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. The associations between the TNF-α-308G/A SNP and CRC risk were examined through conditional logistic regression models adjusted for multiple possible confounding (third) variables. Further, the associations between this SNP and various clinico-pathological parameters, demographic variables and environmental factors within the case group subjects with regard to CRC risk were also evaluated.ResultsThe association between the TNF-α-308G/A SNP and the modulation of risk of CRC was not found to be significant (p value = 0.156). The effect of less common TNF-α-308A allele on the risk of colorectal cancer was also not found to be significant (p value = 0.175). The variant genotype (AA) was nonexistent in the study population. Further, we found no significant effect modulation of CRC risk by wild and heterozygous TNF-α-308G/A SNP genotypes in presence of different possible risk factors (p > 0.05). We also found no significant association of TNF-α-308G/A SNP with the subsets of various characteristics of the case group subjects under study (p > 0.05).ConclusionsThis study indicates that there is no significant association between the TNF-α-308G/A promoter SNP and the risk of developing CRC in ethnic Kashmiri population. However, in order to substantiate our findings, this study needs to be replicated with bigger sample size and should involve other ethnically defined populations with high CRC risk.

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: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.

Dataset Information

Tumor necrosis factor-alpha -308G/A gene polymorphism and novel biomarker profiles in patients with Takayasu arteritis.

Publications

Tumor necrosis factor-alpha -308G/A gene polymorphism and novel biomarker profiles in patients with Takayasu arteritis.

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