Positively Selected G6PD-Mahidol Mutation Reduces Plasmodium vivax Density in Southeast Asians

Chalisa Louicharoen (1, 2) , Etienne Patin (3) , Richard Paul (1) , Issarang Nuchprayoon (2) , Bhee Witoonpanich (1) , Chayanon Peerapittayamongkol (1) , Isabelle Casademont (1) , Thanyachai Sura (4) , Nan M. Laird (5) , Pratap Singhasivanon (4) , Lluis Quintana-Murci (3) , Anavaj Sakuntabhai (1, 4)

1 Génétique de la Réponse aux Infections chez l'Homme
2 Chulalongkorn University [Bangkok]
3 Génétique Evolutive Humaine - Human Evolutionary Genetics
4 Mahidol University [Bangkok]
5 Harvard School of Public Health

Glucose-6-phosphate dehydrogenase (G6PD) deficiency—the most common known enzymopathy—is associated with neonatal jaundice and hemolytic anemia usually after exposure to certain infections, foods, or medications. Although G6PD-deficient alleles appear to confer a protective effect against malaria, the link with clinical protection from Plasmodium infection remains unclear. We investigated the effect of a common G6PD deficiency variant in Southeast Asia—the G6PD-Mahidol487A variant—on human survival related to vivax and falciparum malaria. Our results show that strong and recent positive selection has targeted the Mahidol variant over the past 1500 years. We found that the G6PD-Mahidol487A variant reduces vivax, but not falciparum, parasite density in humans, which indicates that Plasmodium vivax has been a driving force behind the strong selective advantage conferred by this mutation.

Domaines: Génétique des populations [q-bio.PE]; Génétique humaine; Maladies infectieuses

Chalisa Louicharoen, Etienne Patin, Richard Paul, Issarang Nuchprayoon, Bhee Witoonpanich, et al.. Positively Selected G6PD-Mahidol Mutation Reduces Plasmodium vivax Density in Southeast Asians. Science, 2009, 326 (5959), pp.1546-1549. ⟨10.1126/science.1178849⟩. ⟨hal-02352830⟩