TLR9 variant -1237C/C is associated with high parasitaemia in Plasmodium vivax malaria in the Brazilian Amazon population

Background: The Plasmodium vivax malaria (Pv-malaria) is still considered a neglected disease despite an alarming number of individuals are infected yearly. The inflammatory response resulting from the pathogenesis of the disease is closely related to the level of parasitaemia and the genetic background of the host. Genetic polymorphisms in TLRs are involved in the susceptibility or resistance to infection and the identification of genes involved with Pv-malaria response are important to elucidate the pathogenesis of the disease and, may contribute to the formulation of control and elimination tools. Methods: A retrospective case-control study was conducted in an intense transmission area of Pv-malaria in the Amazonas State of Brazil. Genetics polymorphisms in different TLRs and, CD14 molecules were genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) analysis in 325 patients with infected Plasmodium vivax and, 274 healthy individuals without malaria history in the last 12 months. Parasites load was determined by qPCR assay. Simple and multiple linear regressions were performed to investigate association between the polymorphisms and the high parasitaemia of Pv-malaria. Results: Fever (p=0.001) and the C/C genotype of the TLR9 -1237C/T (p=0.014) were independently associated with increased parasitaemia in patients with Pv-malaria. Conclusions: TLR9 variant -1237C/C is associated to high parasitaemia in Pv-malaria. However, additional studies should be conducted in other endemic areas, to confirm the role of host genetics in pathogenesis of Pv-malaria.