[Biochemical basis of the ABO system subgroups]

This review article offers a survey of the biochemical and molecular biological basis of the ABO subgroups. In contrast to protein-based blood groups, the antigens of the ABO system are carbohydrate antigens. The determinant carbohydrate structures are synthesised stepwise by the action of glycosyltransferases which transfer single monosaccharide residues onto an appropriate precursor substance. The genes responsible for the formation of the antigens of the ABO system (viz. ABO, Hh, and Sese) each encode single glycosyltransferases. Sequence analyses have shown that mutations in the ABO gene affecting only two amino acids in the encoded glycosyltransferase decide whether A or B epitope is synthesised. In blood group O individuals several inactive alleles of the ABO locus have been detected, which encode inactive transferases. These mutilated enzymes are not able to synthesise a defined blood group specificity. Blood group O is therefore characterised by the presence of unchanged A and B precursor, i.e. H-substance. Similarly, inactive variants of the H gene are responsible for the rare 'Bombay' phenotype and inactive variants of the secretor gene (Se) are responsible for the non-secretor status. In both cases the mutant transferases are not able to synthesise H-substances.