DEFICIENCY OF 2 RED-CELL FLAVIN ENZYMES IN A POPULATION IN SARDINIA -WAS GLUTATHIONE-REDUCTASE DEFICIENCY SPECIFICALLY SELECTED FOR BY MALARIA

In two areas in Italy where malaria was endemic-in the Po delta and Ma remma on the west coast-we have found a high prevalence of an inherite d flavin-deficient red cell in the normal population, suggesting selec tion by malaria. This study in Sardinia enabled a direct comparison of red-cell activities of FAD-dependent glutathione reductase (EGR) and FMN-dependent pyridoxine phosphate (PNP) oxidase in an ethnically homo geneous population, between two coastal villages where malaria was end emic from 300 B.C. and two mountain villages with no history of malari a. Both enzyme activities were significantly lower on the coast, and i t did not seem that this could be explained by possible small differen ces in dietary riboflavin. As was thought to be the case in Ferrara an d Grosseto, it is probable that a genetically controlled flavin-defici ent red cell was selected for by malaria. Low EGR apoenzyme activity w as more common on the coast, usually explaining the accompanying low b asic EGR activity, and may also have been selected for by malaria. Thi s adds to evidence from others that the mechanism of defence of a flav in-deficient red cell against malaria may be through EGR deficiency. I t could also play a part in the protection given by heterozygous beta- thalassemia. The multifactorial protection of the population against m alaria is discussed.