Report

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

Science  11 Dec 2009:
Vol. 326, Issue 5959, pp. 1546-1549
DOI: 10.1126/science.1178849

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Abstract

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.

  • * These authors contributed equally to this work.

  • Present address: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, U550, Necker Medical School, 75015 Paris, France.

  • Present address: Institut Pasteur, Unité de Pathogénie Virale, 75724 Paris, France.

  • § Present address: Department of Biochemistry, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.

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