title: Positively selected G6PD-Mahidol mutation reduces Plasmodium vivax density in Southeast Asians.
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-Mahidol(487A) 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-Mahidol(487A) 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.
authors.affiliation: Institut Pasteur, Laboratoire de la Génétique de la réponse aux infections chez l'homme, 75724 Paris, France.
authors.forename: Chalisa
authors.initials: C
authors.lastname: Louicharoen
authors.forename: Etienne
authors.initials: E
authors.lastname: Patin
authors.forename: Richard
authors.initials: R
authors.lastname: Paul
authors.forename: Issarang
authors.initials: I
authors.lastname: Nuchprayoon
authors.forename: Bhee
authors.initials: B
authors.lastname: Witoonpanich
authors.forename: Chayanon
authors.initials: C
authors.lastname: Peerapittayamongkol
authors.forename: Isabelle
authors.initials: I
authors.lastname: Casademont
authors.forename: Thanyachai
authors.initials: T
authors.lastname: Sura
authors.forename: Nan M
authors.initials: NM
authors.lastname: Laird
authors.forename: Pratap
authors.initials: P
authors.lastname: Singhasivanon
authors.forename: Lluis
authors.initials: L
authors.lastname: Quintana-Murci
authors.forename: Anavaj
authors.initials: A
authors.lastname: Sakuntabhai
mesh_terms: D000375:Aging; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D005260:Female; D018628:Gene Dosage; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics*; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000097:blood / Q000150:complications / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007113:Immunity, Innate; D016778:Malaria, Falciparum / Q000150:complications / Q000235:genetics / Q000469:parasitology; D016780:Malaria, Vivax / Q000150:complications / Q000235:genetics / Q000469:parasitology*; D008297:Male; D009154:Mutation; D010963:Plasmodium falciparum / Q000502:physiology; D010966:Plasmodium vivax / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D013785:Thailand
chemical_list: D005954:Glucosephosphate Dehydrogenase