Molecular genotyping of Plasmodium species erythrocyte receptors

Background

Plasmodium falciparum merozoite invasion of host erythrocytes is a virulence factor, since parasites that successfully invade erythrocytes can proliferate and therefore determine the clinical outcome of an infection. Thus, merozoite proteins are the focus of experimental malaria vaccines, as antibodies to these proteins can inhibit invasion, resulting in the prevention of disease. However, the merozoite proteins are present as multiple alleles, allowing for multiple redundant and alternative invasion pathways, which offer a survival advantage to the parasite. Conversely, the differences in host receptors can alter the virulence capability of the parasite. The classic case in point is the Duffy antigen, in West Africa where the population is Duffy negative they are resistant to P. vivax infections. A number of merozoite protein-erythrocyte receptor interactions have been identified, such as the erythrocyte binding antigen 175 with glycophorin A on the erythrocyte surface. Nevertheless, the available data on the polymorphisms of known erythrocyte receptors in African populations is minimal. Therefore, interrogating the erythrocyte receptor polymorphisms in malaria endemic populations, allows us to define variants that have evolved as a result of exposure to malaria, which may therefore confer a mechanism of resistance or susceptibility to infection.

Objectives

1. To define the polymorphisms in human erythrocyte receptors, glycophorin A, B, C/D, E, band 3, DARC, Basigin and CR1.
2. To determine if the polymorphisms in the 8 genes are under any selective pressure.
3. To identify genetic combinations between merozoite and erythrocyte genotype pairs.