A role for G6PD Mahidol in Protection against malaria in Southeast Asia

Abstract

Glucose-6-phosphate dehydrogenase (G6PD) deficiency causes neonatal jaundice and hemolytic anemia and affects over 400 million people worldwide. The protective effect against malaria conferred by G6PD deficiency alleles has been proposed, yet the link with clinical protection from Plasmodium falciparum and Plasmodium vivax remains inconclusive. Here I investigated the impact on human survival of a common G6PD deficiency mutation in Southeast Asia – G6PD Mahidol487A – from P. vivax and P. falciparum malaria. My results indicate that strong and recent positive selection has targeted G6PD Mahidol487A mutation for the last 1,500 years with the selection intensity 0.23. In addition, I provide evidence that P. vivax has been the agent responsible for the strong selective advantage conferred by the G6PD-Mahidol487A, because it reduces P. vivax parasite density, but not P. falciparum, in the host. These findings support the notion that P. vivax historically had a considerable impact on human health, at least in South-East Asia.