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G6PD deficiency is associated with significant protection against severe, life-threatening malaria

A case-control study in two populations in Mali, West Africa has shown that glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with significant protection against severe, life-threatening malaria.

Researchers from the US National Institute of Allergy and Infectious Diseases and the University of Bamako, Mali, led by Thomas E. Wellems, report the findings this week in the open access journal PLoS Medicine.

G6PD deficiency is also known as “favism” after the Italian word for broad beans (fava) which cause a classic reaction when eaten by people with G6PD deficiency. In males, who have only one X chromosome, mutations in the gene for G6PD on the X chromosome cause G6PD deficiency. Females who have mutations on both X chromosomes will also be deficient. G6PD is an important enzyme in red blood cells (erythrocytes), the host cells for Plasmodium falciparum, the parasite that causes the most severe form of malaria. G6PD deficiency is associated with protection against malaria, notably in Africa where one form of G6PD deficiency (G6PD A-) is widespread.

In the two populations of more than 3000 children studied in rural Mali where malaria is very frequent, G6PD deficiency in male and female children was associated with protection against severe, life-threatening malaria, but no effect was found in females who had just one abnormal gene. However, there was no significant difference in the numbers of parasites in the red blood cells of the various groups of children indicating that the deficiency does not work by stopping parasites from infecting the children. G6PD deficiency instead appears to mitigate disease processes set up by the parasitized cells in the bloodstream. The protection was confirmed by a combined analysis of these data and data from a previous study. Protection was most evident against cerebral malaria, the most frequent form of life-threatening malaria in these studies.

These results reignite the debate about the relationship between G6PD deficiency and protection against malaria. They are particularly relevant in populations such as the one studied where, as the authors note, because “virtually all young children experience episodes of malaria, such protective hemoglobinopathies and erythrocyte polymorphisms offer a tremendous survival benefit when they prevent progression of uncomplicated malaria.”

Andrew Hyde | EurekAlert!
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