GLUCOSE-6-PHOSPHATE DEHYDROGENASE AND MALARIA: GREATER RESISTANCE OF FEMALES HETEROZYGOUS FOR ENZYME DEFICIENCY AND OF MALES WITH NON-DEFICIENT VARIANT

Abstract In 700 children of both sexes from a rural area of holo-endemic malaria ( P. falciparum ), who presented to hospital because of an acute febrile illness, we have determined the parasite rate, the parasite density, and the genotype for the red-cell enzyme, glucose-6-phosphate dehydrogenase. In males, there was no evidence that enzyme-deficient subjects have any greater resistance against malaria than normal subjects. However, amongst non-deficient male subjects, those with the electrophoretic variant A of glucose-6-phosphate dehydrogenase have significantly lower parasite counts than those with the B variant of the enzyme. In females , homozygous deficient subjects again show no evidence of protection. However, subjects heterozygous for glucose-6-phosphate-dehydrogenase deficiency (specifically, those with the G d A- /G d B genotype) have significantly lower parasite counts than any other group of females or males. We conclude that the high frequency of the gene for the non-deficient variant A in the population studied is probably maintained by the advantage against malaria selection of hemizygous males (and perhaps of homozygous females). The high frequency of the glucose-6-phosphate-dehydrogenase deficiency gene is maintained mainly, and perhaps entirely, by the advantage against malaria of heterozygous females.