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 certain types of cancer but also exhibit strong
susceptibility to malaria tropica or infection by <i>Plasmodium falciparum</i>.
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<i> O</i>-GalNAc glycosylation of the
parasite's serine repeat antigen (SERA). 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-<i>O</i>-Ser/Thr-R glycosylations.