gms | German Medical Science

The impact of host genetics on resistance and susceptibility to Plasmodium falciparum malaria has been intensively investigated over the past two decades. There is increasing evidence that malaria parasites have shaped the human genome in endemic regions with strong selective pressure. Various genes have been identified which are associated with malaria phenotypes. Factors that promote manifestations of malaria comprise parasitemia level, parasite induced inflammation, sequestration and anemia of infected erythrocytes in organ microvasculature, in particular in the brain. Advances in genomic research technologies such as genome-wide association studies (GWAS) and fine genotyping techniques have enabled the uncovering of a number of genetic polymorphisms that justify further studies in host-parasite interactions.

Human gene variants identified so far will be described and discussed that have been demonstrated to be associated with protection or susceptibility to falciparum malaria. Although some polymorphisms have a significant impact for the course of Plasmodium infection and malaria, other findings are indecisive or even contradictory and should be considered with caution. The discovery of genetic polymorphisms associated with various diseases phenotypes may help to understand the pathophysiology of malaria and facilitate the development of prevention measures or treatments. Heterogeneity of human populations as well as environmental effects can affect the diversity of clinical malaria, thus warranting further research with the aim of developing and evaluating new interventions, therapies and better management against falciparum malaria.