Central position of the human histo (blood) group O(H) and phenotype-determining enzymes in growth and infectious disease
The human ABO(H) blood phenotypes arise from the evolutionarily oldest genetic system found in primate populations, but arise in critical molecular complementarity with distinct eukaryotic and prokaryotic pathogens, while the development of non-O(H) phenotypes is associated with the impaired formation of adaptive and innate immunoglobulin specificities. Indeed, compared with individuals with blood group O(H), individuals with blood group A not only have significantly higher risk of developing
... isk of developing certain types of cancer but also exhibit strong susceptibility to malaria tropica or infection by Plasmodium falciparum. Thus, the phenotype-determining glycotransferase(s) from blood group A, affecting the levels of anti-A/Tn cross-reactive immunoglobulins in phenotypic glycosidic accommodation, might also complete adhesion and entry of the parasite to host cells via trans-species O-GalNAc glycosylation of the parasite's serine repeat antigen (SERA), thereby excluding the antibody formation against it. In contrast, human blood group O(H), lacking this enzyme, is discussed to have a survival advantage of the overall risk of developing cancer and rarely develops life-threatening infection by evolutionary selective malaria strains, which on the other side may interfere with the growth of cancer by competition with A-like/Tn, developmental GalNAcα1-O-Ser/Thr-R glycosylations.