Mutant NO Gene Protects Against Malaria

Researchers have found that a mutation resulting in increased production of nitric oxide protects children against two of the most severe manifestations of childhood malaria, cerebral malaria and severe malarial anemia. Their finding was reported in the November 9, 2002, issue of The Lancet.

Nitric oxide (NO) is toxic to malaria parasites in vitro and protects rodents from disease in vivo. The induction and regulation of the human nitric oxide synthase type 2 (NOS2) gene, which controls synthesis of NO from its substrate L-arginine, is complex and involves sequences of up to 16 kb upstream of the gene.

An international research team studied 179 children in coastal Tanzania, with and without cerebral malaria. They found that children with a variant of NOS2 that allowed them to make greater amounts of nitric oxide were 88% less likely to develop cerebral malaria than were those without the variant. The researchers then examined DNA collected through a U.S. Centers for Disease Control study of 1,106 children in Kenya. They found that the same NOS2 variant protected the Kenyan children from severe malarial anemia as well as from cerebral malaria.

"This is a major advance in understanding how and why children get the deadliest forms of malaria,” said senior author Dr. Brice Weinberg from Duke University (Durham, NC, USA).

The authors suggest that targeted interventions to increase NO delivery or production could provide novel preventive and therapeutic strategies against these major causes of mortality in African children.




Related Links:
Duke University