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.
Highlights
The influence of host genetics on susceptibility to Plasmodium falciparum malaria has been extensively studied over the past twenty years
Host genetic factors contribute to the variability of malaria phenotypes [3] and should help to determine some of the mechanisms involved in susceptibility to P. falciparum infection
The results suggest that T-regulatory cell activity could be central in the control of malaria infection in populations exposed to naturally high P. falciparum transmission
Summary
It is clear that genetically-based alterations conferring protection against malaria have led to co-adaptation of various human populations with widespread malaria parasites. A global collaborative effort or consortium must be made to collect information about involvements of biomarkers in malaria susceptibility. This collaboration should include phenotype and clinical data as well as genomics, proteomics, metabolomics and parasitomics. Additional file 1: Review of gene polymorphisms reported to date to be significantly associated the host phenotype of susceptibility/ resistance to P. falciparum malaria. Author details 1Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, Georgia, USA. Competing interests The authors declare that they have no competing interests
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