Host Genetic Variants That Protect Against Clinical Malaria May Influence Asymptomatic Malaria Parasite Carriage

Abstract

The outcome of a Plasmodium falciparum infection is influenced by host genetic factors. The relationship between host genetics and severe malaria has been studied more intensely than the relationship between host genetics and the more common mild and asymptomatic malarias. With a global change of focus from malaria control to elimination, there is the obvious need to understand and target all forms of the disease, particularly asymptomatic malaria, with its high burden and transmission potential. The Candidate Gene Approach was used to test the hypothesis that symptomatic Malaria-Protection Associated Single Nucleotide Polymorphisms (SNPs) were associated with protection against asymptomatic parasite density. Five SNPs, Toll-Like Receptor 4 (TLR 4)-Asp299Gly (A>G), Nitric Oxide Synthase (NOS2)-954 G>C, Interleukin 10 (IL 10)-592 A>C, Mannose Binding Lectin (MBL2) G230A and Interferon-gamma (IFN-γ)+874 T>A. These SNPs, with “pro-parasitic” and antiparasitic effects in symptomatic malaria, were genotyped by Restriction Fragment Length Polymorphism and sanger sequencing and tested for associations with asymptomatic P. falciparum parasite density, as detected by Photo-Induced Electron Transfer Polymerase Chain Reaction, in school-going children in Simiw, Ghana. IFN-γ+874 T>A was associated with a lower asymptomatic parasite density while MBL2 G230A was monomorphic in the population. According to these results, a host genetic influence on asymptomatic malaria parasite density does exist, partly overlapping that of clinical malaria infections. Parasitic immunity among the malarias may share a similar, yet complex immunogenetics despite their differences in symptomatic severity.