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, I2 = 0%) or homozygous model (OR: 1.55, 95% CI: 1.08-2.28, I2 = 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, I2 = 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, I2 = 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, I2=85%) and homozygous model (OR: 1.49, 95% CI: 1.09-2.0, I2 = 0%). For TLR4 (D299G, T399I), none is significantly associated with either severity of malaria or susceptibility to malaria under any genetic models.
CONCLUSIONS: The findings suggest that TLR 9 (T1486C and T1237C) seems to influence the progression of malaria, under certain genetic models and in specific age group of people from specific geographical region. TLR 9 (T1237C) also plays a role in susceptibility to malaria under certain genetic models and only with children of non-Asian countries. To substantiate these, future well designed studies with larger samples across endemic countries are needed.