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

Sarangi, Surjyapratap; Nahak, Suraj K; Padhi, Sunali; Nayak, Nisha; Pradhan, Bidyutprabha; Panigrahi, Jogeswar; Panda, Aditya K.

doi:10.1080/15257770.2022.2151622

Cited by 1 publication

(7 citation statements)

References 24 publications

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“…This is the second meta-analysis to address the association between TNF-α -308G >A polymorphisms and the risk of severe P. falciparum malaria and the first metaanalysis to unravel this association in different populations. Contrary to the previous metaanalysis [34], the study failed to reveal an association between TNF-α -308G >A polymorphism and susceptibility to severe P. falciparum malaria in the overall analysis under all genetic models. Moreover, the modifier analyses (excluding the HWE-deviated study) further validated the non-significant association.…”

Section: Discussioncontrasting

confidence: 99%

“…Instead, the significant association was only observed in the racial subgroup. A recent meta-analysis [34] found a significant association between the -308G >A polymorphism and predisposition to the P. falciparum clinical severity in the allele comparison and dominant model. There are several possible reasons for such different results.…”

Section: Novelties Of the Present Meta-analysismentioning

confidence: 99%

“…Table 1 lists the eight case-control studies included in the meta-analysis [26][27][28][29][30][31][32][33]. Of them, five [26,27,29,32,33] were not included (new) in a recent meta-analysis [34]. The year range of the articles was 1994-2019 and comprised 1,448 severe P. falciparum malaria cases and 1,371 uncomplicated malaria control.…”

Section: Characteristics Of the Included Studiesmentioning

confidence: 99%

“…First, the current metaanalysis included five more published studies that were not included in the previous one. In this study, 8 eligible studies with 1,448 cases and 1,371 controls to yield summary statistics, however, Sarangi et al (2023) analyzed data with 982 cases and 773 controls. Second, the malaria phenotype in the control group was not uniform in previous meta-analyses [34].…”

Section: Novelties Of the Present Meta-analysismentioning

confidence: 99%

“…However, the results of these studies [26][27][28][29][30][31][32][33] are conflicting, probably because of small sample sizes and low statistical power. Although recent meta-analysis [34] reported a significant association between TNF-α -308G >A polymorphism and predisposition to severe P. falciparum malaria in the allele and dominant model, there were some obvious limitations in their meta-analytic procedure. First, the subjects in the control group consisted of heterogenous phenotypes, including asymptomatic malaria [35], uncomplicated malaria, and other illnesses [36].…”

Section: Introductionmentioning

confidence: 99%

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Tumor necrosis factor-α (TNF-α) -308G >a promoter polymorphism (rs1800629) promotes Asians in susceptibility to Plasmodium falciparum severe malaria: A meta-analysis

Kongjam,

Pabalan,

Tharabenjasin

et al. 2023

PLoS Negl Trop Dis

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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.

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Section: Discussioncontrasting

confidence: 99%

Section: Novelties Of the Present Meta-analysismentioning

confidence: 99%