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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: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.

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.

Similar Datasets

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