The host genetic diversity in malaria infection

Abstract

Populations exposed to Plasmodium infection develop genetic mechanisms of protection against severe disease. The clinical manifestation of malaria results primarily from the lysis of infected erythrocytes and subsequent immune and inflammatory responses. Herein, we review the genetic alterations associated with erythrocytes or mediators of the immune system, which might influence malaria outcome. Moreover, polymorphisms in genes related to molecules involved in mechanisms of cytoadherence and their influence on malaria pathology are also discussed. The results of some studies have suggested that the combinatorial effects of a set of genetic factors in the erythrocyte-immunology pathway might be relevant to host resistance or susceptibility against Plasmodium infection. However, these results must be interpreted with caution because of the differences observed in the functionality and frequency of polymorphisms within different populations. With the recent advances in molecular biology techniques, more robust studies with reliable data have been reported, and the results of these studies have identified individual genetic factors for consideration in preventing severe disease and the individual response to treatment.

Figure 1

Influence of erythrocyte and immune response gene polymorphisms in malaria outcome. The diagram summarizes the major genetic alterations identified in the erythrocyte and immune response pathways that influence malaria outcome. The up arrow indicates susceptibility, and the down arrow indicates resistance to malaria. Contradictory or not confirmed results are represented by red font color. The protective effect of inherited genetic disorders involving the RBC on malaria infection has been associated with membrane cytoskeleton disorders, surface antigen mutations, enzymatic machinery deficiencies, or hemoglobin and its heme prosthetic group alterations. Considering the immune response, several polymorphisms in gene encoding the TLR receptors and in important cytokines involved in malaria immunopathology are described in the literature. Furthermore, genetic alterations in the FcgRIIA receptor and nitric oxide synthase were also associated with resistance/susceptibility to malaria.