A common polymorphism in the mechanosensitive ion channel <i>PIEZO1</i> is associated with protection from severe malaria in humans
Christian N. Nguetse, Natasha Purington, Emily R. Ebel, Bikash Shakya, Marilou Tétard, Peter G. Kremsner, Thirumalaisamy P. Velavan, Elizabeth S. Egan
Abstract
Significance The clinical presentation of Plasmodium falciparum malaria as severe versus uncomplicated is influenced by host genetic factors. Recently, a gain-of-function mutation in the mechanosensitive ion channel PIEZO1 was shown to protect mice against cerebral malaria, but its role in human malaria is unknown. Here we investigated a common PIEZO1 variant that encodes a mild gain-of-function mutant in human erythrocytes, and show that it is associated with malaria protection in Gabonese children. We found an epistatic relationship between PIEZO1 E756del and the sickle cell trait. While parasite growth and cell hydration were normal, surface expression of PfEMP-1 was reduced in the mutant cells. Understanding the link between common PIEZO1 variants and malaria susceptibility may yield new therapies for malaria.