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

TLDR: The evidence indicating that all glucose-6-phosphate dehydrogenase (G6PD) deficient genotypes are relatively pro- tected against Plasmodium falciparum malaria is reviewed.

Abstract: 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 pro-vide 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 un-derlie 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 en- hanced 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. € 1993 Wiley-Liss, Inc. The specific goal of this article is to review the evidence indicating that all glucose-6-phosphate dehydrogenase (G6PD) deficient genotypes are relatively pro- tected against Plasmodium falciparum malaria. A discussion of this issue is timely and necessary because several influential reviews of G6PD and G6PD deficiency in the medical literature over the past few years have reiterated the position that only G6PD deficient heterozygotes are protected against falciparum parasitization, while G6PD deficient hemizygotes and homozygotes are not (Luzzatto and Mehta, 1989; Luzzatto and Battistuzzi, 1985; Usanga and Luzzatto, 1985). However, this position is based on a single study (Bienzle et al., 1972), while a number of other field investigations support the view that all G6PD deficient genotypes are rela- tively protected against falciparum parasitization (Allison and Clyde, 1961; Gilles et al., 1967; Butler, 1973; Kar et al., 1992). The inaccuracy of the "heterozygote" position seriously obscures our understanding of how selection operates at the