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Pyruvate Kinase Deficiency Protects Against Malaria

Mutant alleles may have conferred relative survival advantage against the parasite

WEDNESDAY, April 16 (HealthDay News) -- Individuals with pyruvate kinase deficiency enjoy protection against malaria caused by Plasmodium falciparum, suggesting that mutant pyruvate kinase alleles may have contributed to a relative survival advantage against malaria in endemic areas, according to an article published online April 16 in the New England Journal of Medicine.

Kodjo Ayi, Ph.D., of the University of Toronto in Toronto, Canada, and colleagues analyzed DNA from three individuals with pyruvate kinase deficiency and their relatives to characterize gene mutations. In addition, the researchers infected erythrocytes from case subjects and controls with P. falciparum isolates in vitro and assessed invasion and maturation at various time points. Macrophage clearance of ring-stage infected erythrocytes was also assessed.

Homozygous mutations in the gene for pyruvate kinase (PKLR) were seen in the three subjects, and the erythrocytes of these individuals exhibited reduced invasion of P. falciparum parasites compared to controls. In addition, clearance of ring-stage infected erythrocytes by macrophages was enhanced in case subjects compared to controls, the researchers report. No significant differences in intracellular maturation of parasites were seen in case subjects compared to controls.

"An examination of the action of selection pressure on pyruvate kinase could shed light on the history and mechanism of human resistance to malaria," write the authors of an associated editorial.

This study was partially funded by Genome Canada.

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