G6PD deficiency as protection againstfalciparum malaria: An epidemiologic critique of population and experimental studies

Several recent reviews in the medical literature maintain that only heterozygous G6PD deficient females are relatively protected against falciparum malaria. However, a number of population studies provide compelling evidence that both the hemizygous G6PD deficient male and homozygous G6PD deficient female are also relatively protected against falciparum parasitization. An epidemiologic critique of a sample of these field investigations points out the methodological problems that underlie some of the negative findings. In vitro studies also provide compelling evidence that erythrocytes from all G6PD deficient genotypes are relatively protected against falciparum infestation, and that this protection is enhanced by oxidant substances derived from a number of food crops such as fava beans. It is suggested that “quinine” taste sensitivity reflects taste sensitivity to bitter-tasting, naturally occurring antimalarial substances of plant origin, and that the G6PD polymorphism and the genetic loci coding for “quinine” taste sensitivity have co-evolved in human populations. It appears that adaptation at the G6PD locus in human populations reflects an intricate web of interactions between a large number of different G6PD deficient alleles which have reached polymorphic frequencies and a variety of food crops from which oxidant substances may be derived.