The contribution of human erythrocyte polymorphisms in the protection against malaria

Abstract

ABSTRACT

The understanding of the complex life cycle of malaria has greatly improved in the last few years, however, despite decades of research and struggle against the disease, it continues to be a major public health problem, especially in the poorest areas of the world. Due to its long-term high prevalence in certain regions of the globe, malaria has exerted strong selective pressure on the human genome. The genetic component of malaria susceptibility is complex, with a variety of polymorphisms influencing both pathogenesis and host response. Evaluating these determinants of susceptibility and deciphering the mechanisms involved may lead to the discovery of new vaccines or targets for pharmacological agents. The most common and best characterized human genetic polymorphisms that confer protection against malaria involve specific structural erythrocyte proteins (such as haemoglobin S and C, thalassemias, the Duffy antigen, and blood group O) and enzymes (such as glucose-6-phosphate dehydrogenase deficiency and, more recently described, pyruvate kinase deficiency). This short review describes these genetic variants, reviews some of the controversial results that have been obtained, and discusses mechanisms that might explain the protection they provide.