# New Evidence of TLR4 and TLR9 Variants Influencing Parasitaemia and Symptoms of Plasmodium vivax Infection

## TL;DR

This study finds that genetic variants in TLR4 and TLR9 are linked to higher parasite levels and more severe symptoms in P. vivax malaria in the Brazilian Amazon.

## Contribution

First evidence of TLR4 rs1927911 variant's association with P. vivax symptoms in the Brazilian Amazonian population.

## Key findings

- TLR9 rs352140TT homozygotes had higher parasitaemia levels than C allele carriers.
- TLR4 rs1927911GG homozygotes had a higher clinical index than A allele carriers.

## Abstract

Toll‐like receptors (TLRs) induce the production of pro‐inflammatory cytokines and regulate the immune response to Plasmodium vivax infection. Genetic variants of TLRs are associated with susceptibility and severity of malaria in different populations. This study aimed to evaluate the association between polymorphisms in TLR1, TLR4, TLR7, TLR8, TLR9 and TIRAP and the clinical manifestations of malaria caused by P. vivax in a population from the Amazon region of Pará, Brazil. A total of 148 individuals with symptomatic uncomplicated malaria were genotyped for rs4833095, rs1927911, rs179008, rs3764880, rs352140 and rs8177374 variants, and their associations with parasitaemia levels, gametocytaemia and clinical index were analysed using generalised linear models. TLR9 rs352140TT homozygotes had higher parasitaemia levels than C allele carriers (p = 0.034). TLR4 rs1927911GG homozygotes had a higher clinical index than A allele carriers (p = 0.018). Our results describe, for the first time, the association of the rs1927911 variant found in intron 1 of TLR4 with P. vivax malaria symptoms in Brazilian Amazonian population.