Genetic polymorphisms linked to susceptibility to malaria

Abstract

The influence of host genetics on susceptibility to Plasmodium falciparum malaria has been extensively studied over the past twenty years. It is now clear that malaria parasites have imposed strong selective forces on the human genome in endemic regions. Different genes have been identified that are associated with different malaria related phenotypes. Factors that promote severity of malaria include parasitaemia, parasite induced inflammation, anaemia and sequestration of parasitized erythrocytes in brain microvasculature.Recent advances in human genome research technologies such as genome-wide association studies (GWAS) and fine genotyping tools have enabled the discovery of several genetic polymorphisms and biomarkers that warrant further study in host-parasite interactions. This review describes and discusses human gene polymorphisms identified thus far that have been shown to be associated with susceptibility or resistance to P. falciparum malaria. Although some polymorphisms play significant roles in susceptibility to malaria, several findings are inconclusive and contradictory and must be considered with caution. The discovery of genetic markers associated with different malaria phenotypes will help elucidate the pathophysiology of malaria and enable development of interventions or cures. Diversity in human populations as well as environmental effects can influence the clinical heterogeneity of malaria, thus warranting further investigations with a goal of developing new interventions, therapies and better management against malaria.

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“…This mechanism act as natural selection and is co-responsible for the high prevalence of HbS in malaria endemic regions as a result of natural selection over generations [9].…”

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“…The observations that antimalarial treatment efficacy depends not only on intrinsic drug activity, but also on age as well as on transmission intensity indicates additional host factors are involved in shaping the treatment outcome. 7,8,12 Sulphadoxinepyrimethamine clearance of malaria infections was shown to be enhanced in individuals heterozygous for the sickle cell trait (HbAS) compared to individuals with the normal hemoglobin form (HbAA). 42 The authors found those with HBAS at reduced risk of treatment failure by day 7 post-drug treatment among all age groups and particularly in children below 6 months, an observation which could partially be explained by materno-foetal transfer of antimalarial antibodies during birth.…”

NOS2 Variants Reveal a Dual Genetic Control of Nitric Oxide Levels, Susceptibility to Plasmodium Infection, and Cerebral Malaria

“…Nevertheless, the exact role of genetic variance in inflammatory responses against Plasmodium infection and in malaria severity remains unclear (1). It is possible that innate immunity genes associated to malaria may play a dual role in the course of infection.…”

“…Genetic evidence accumulated in recent years supports a complex role for host genetics in resistance and susceptibility to human malaria (2). Hemoglobin gene variants are well-known malaria resistance factors, but a considerable number of genetic studies focused on clinical malaria syndromes and blood parasite burden also highlighted genes involved in the immune response, inflammation, and cell adhesion (1).…”

“…Inflammatory responses are determinants of the clinical course of infection and are influenced by host genetic factors (1). Genetic evidence accumulated in recent years supports a complex role for host genetics in resistance and susceptibility to human malaria (2).…”