Exploring putative molecular mechanisms of human pyruvate kinase enzyme deficiency and its role in resistance against Plasmodium falciparum malaria.

Abstract

Malaria is the third most prevalent cause of global mortality and is an interesting case of evolutionary selection. In response to high frequency of malaria infection, several host genetic factors have been selected, such as Hemoglobin variants, Glucose-6-phosphate dehydrogenase (G6PD) deficiency and pyruvate kinase deficiency. Among these popular host genetic factors, deficiency of pyruvate kinase enzyme is one of the most important factor that provide resistance against malaria. Regulation of this enzyme at the level of transcription is important and several factors may play crucial role in regulation of this enzyme. DNA sequence variation and epigenetic factors modifying transcriptional regulation of gene have been explored in context of several diseases. In the present study, we explored the factors modifying transcription regulation of pyruvate kinase gene with the help of Bioinformatics tools. On the basis of our predictions we hypothesize that any factor that reduces the availability (level) or activity of pyruvate kinase enzyme must play a strong role in resistance to malaria. Thus, factors reducing the activity (loss of function) or level of pyruvate kinase have been selected to provide resistance against malaria primarily in endemic regions.