Toll-like receptor 9 and 4 gene polymorphisms in susceptibility and severity of malaria: a meta-analysis of genetic association studies

• Published in: Malaria Journal
• Main Authors: Cho Naing, Siew Tung Wong, Htar Htar Aung
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2021
• Subjects: Toll-like receptor; Polymorphisms; Severity; Susceptibility; Malaria; Meta-analysis; Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1186/s12936-021-03836-6; https://doaj.org/article/cd3888b1250246338f5b4ddcf2ccffaa

Abstract Background Malaria is still a major public health problem in sub-Saharan Africa and South-east Asia. The clinical presentations of malaria infection vary from a mild febrile illness to life-threatening severe malaria. Toll like receptors (TLRs) are postulated to be involved in the innate immune responses to malaria. Individual studies showed inconclusive findings. This study aimed to assess the role of TLR4 (D299G, T399I) and TLR9 (T1237C, T1486C) in severity or susceptibility of malaria by meta-analysis of data from eligible studies. Methods Relevant case–control studies that assessed the association between TLR 4/9 and malaria either in susceptibility or progression were searched in health-related electronic databases. Quality of included studies was evaluated with Newcastle–Ottawa scale. Pooled analyses for specific genetic polymorphisms were done under five genetic models. Stratified analysis was done by age and geographical region (Asian countries vs non-Asian countries). Results Eleven studies (2716 cases and 2376 controls) from nine endemic countries were identified. Five studies (45.4%) obtained high score in quality assessment. Overall, a significant association between TLR9 (T1486C) and severity of malaria is observed in allele model (OR: 1.26, 95% CI: 1.08–1.48, I 2 = 0%) or homozygous model (OR: 1.55, 95% CI: 1.08–2.28, I 2 = 0%). For TLR9 (T1237C), a significant association with severity of malaria is observed in in heterozygous model (OR:1.89, 95% CI: 1.11–3.22, I 2 = 75%). On stratifications, TLR9 (T1486C) is only significantly associated with a subgroup of children of non-Asian countries under allele model (OR: 1.25, 95% CI: 1.02–1.38), while 1237 is with a subgroup of adults from Asian countries under heterozygous model (OR: 2.0, 95% CI: 1.09–3.64, I 2 = 39%). Regarding the susceptibility to malaria, TLR9 (T1237C) is significantly associated only with the children group under recessive model (OR: 2.21, 95% CI: 1.06–4.57, I 2=85%) and homozygous model (OR: 1.49, 95% CI: 1.09–2.0, I 2 = ...