TNF-α promoter variant (G-308A) is associated with susceptibility to P. falciparum infection and severe malaria: a meta-analysis and trial sequential analysis

Abstract

Tumor necrosis factor-alpha (TNF-α) plays an essential role in Plasmodium falciparum infection, with lower levels associated with susceptibility to infection and higher levels linked with organ failure in severe malaria. Genetic polymorphisms in the promoter region of the TNF-α gene (G-308A and G-238A) affect plasma TNF-α levels. Numerous case-control studies have been conducted to determine the possible association between TNF-α polymorphisms and susceptibility to malaria infection and clinical severity; however, the results are inconsistent. Various databases such as Google Scholar, Science Direct, PubMed, and Scopus were searched for relevant articles for the present meta-analysis. Data were extracted from the eligible studies based on inclusion and exclusion criteria. Meta-analysis was carried out with CMA v.3.3.070 software, and combined odds ratio, 95% confidence interval, and p values were calculated. Further, a trial sequential analysis was also performed to test whether enough number of case and controls have been enrolled to date to draw a valid conclusion. Allele (OR = 9.757, p value=.049) and heterozygous (OR = 8.98, p value=.016) comparison model revealed the TNF-α G-308A variant as a susceptible genetic factor for P. falciparum infection. Similarly, a significant association of TNF-α G-308A polymorphism with P. falciparum malarial severity was also observed (A versus G: OR = 1.761, p value = .000; and GG + GA versus GG: OR = 1.769, p value = .000). However, no association of TNF-α (G-238A) polymorphism was observed with infection and severity of P. falciparum or Plasmodium vivax malaria. TNF-α G-308A variant is associated with susceptibility to P. falciparum infection and clinical severity. However, further studies on different populations are required.

Keywords:

• TNF-α
• gene polymorphism
• meta-analysis
• association
• severe malaria
• Plasmodium falciparum

Acknowledgements

Department of Bioscience and Bioinformatics, Berhampur University is supported with the Post Graduate Teaching programme in Biotechnology by the Department of Biotechnology (DBT) Govt. of India. The authors thank the World Bank-OHEPEE (Odisha Higher Education Program for Excellence and Equity), Department of Higher Education, Govt of Odisha to support the Centre of Excellence on Bioprospecting of Ethnopharmaceuticals of Southern Odisha to explore their potential against cancer, infectious and autoimmune diseases to Berhampur University. Abhijit Pati is supported with a Senior Research Fellowship from the Indian Council of Medical Research (ICMR), New Delhi.

Funding statement

No specific fund has been received for this work.