{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T03:11:15Z","timestamp":1780629075355,"version":"3.54.1"},"update-to":[{"DOI":"10.1371\/journal.pntd.0011735","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T00:00:00Z","timestamp":1700179200000}}],"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T00:00:00Z","timestamp":1698796800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Thailand Science Research and Fundamental Fund"},{"DOI":"10.13039\/501100004704","name":"National Research Council of Thailand","doi-asserted-by":"publisher","award":["820\/2563"],"award-info":[{"award-number":["820\/2563"]}],"id":[{"id":"10.13039\/501100004704","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005790","name":"Thammasat University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005790","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Thammasat University Research Fund under Thammasat University Research Scholar"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>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-\u03b1). However, the relationship between <jats:italic>TNF-\u03b1<\/jats:italic> -308G &gt;A gene polymorphism (rs1800629) and the severity of <jats:italic>Plasmodium falciparum<\/jats:italic> (<jats:italic>P<\/jats:italic>. <jats:italic>falciparum<\/jats:italic>) 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 <jats:italic>TNF-\u03b1<\/jats:italic> -308G &gt;A polymorphism was determined in uncomplicated malaria (UM) and severe malaria (SM) of <jats:italic>P<\/jats:italic>. <jats:italic>falciparum<\/jats:italic> 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, <jats:italic>i<\/jats:italic>.<jats:italic>e<\/jats:italic>., 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 <jats:italic>TNF-\u03b1<\/jats:italic> -308G &gt;A polymorphism and susceptibility to <jats:italic>P<\/jats:italic>. <jats:italic>falciparum<\/jats:italic> SM (ORs = 1.10\u20131.52, 95%CIs = 0.68\u20132.79; <jats:italic>P<\/jats:italic><jats:sup>a<\/jats:sup> = 0.24\u20130.68). 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\u20133.61, <jats:italic>P<\/jats:italic><jats:sup>a<\/jats:sup> = 0.03) and codominant (OR = 1.83, 95% CI = 1.15\u20132.92, <jats:italic>P<\/jats:italic><jats:sup>a<\/jats:sup> = 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 <jats:italic>P<\/jats:italic>-value of0.02\u20130.03. The significant core outcomes were robust. Results of the meta-analysis suggest that <jats:italic>TNF-\u03b1<\/jats:italic> -308G &gt;A polymorphism might affect the risk of <jats:italic>P<\/jats:italic>. <jats:italic>falciparum<\/jats:italic> SM, particularly in individuals of Asian descent. This supports ethnicity as one of the dependent factors of the <jats:italic>TNF-\u03b1<\/jats:italic> -308G &gt;A association with the clinical severity of malaria. Further large and well-designed genetic studies are needed to confirm this conclusion.<\/jats:p>","DOI":"10.1371\/journal.pntd.0011735","type":"journal-article","created":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T17:49:55Z","timestamp":1698860995000},"page":"e0011735","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Tumor necrosis factor-\u03b1 (TNF-\u03b1) -308G &gt;a promoter polymorphism (rs1800629) promotes Asians in susceptibility to Plasmodium falciparum severe malaria: A meta-analysis"],"prefix":"10.1371","volume":"17","author":[{"given":"Panida","family":"Kongjam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noel","family":"Pabalan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phuntila","family":"Tharabenjasin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamdi","family":"Jarjanazi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanna","family":"Chaijaroenkul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6389-0897","authenticated-orcid":true,"given":"Kesara","family":"Na-Bangchang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,11,1]]},"reference":[{"key":"pntd.0011735.ref001","doi-asserted-by":"crossref","DOI":"10.30875\/6c551ba0-en","author":"Organization WH","year":"2021","journal-title":"World malaria report 2021"},{"key":"pntd.0011735.ref002","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/BF03160478","article-title":"Polymorphisms in tumor necrosis factor and other cytokines as risks for infectious diseases and the septic syndrome","volume":"3","author":"J. 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