[Molecular background of the ABO blood group system]

The ABO human blood group system consists of A antigens, B antigens, and antibodies against these antigens. The antigenic determinants are synthesized in the Golgi apparatus by specific glycosyltransferases which transfer proper sugars to an oligosaccharide acceptor, called H antigen. N-acetylgalactosaminotransferase (transferase A) uses a UDP-GalNac donor to convert the H antigen to A antigen, whereas galactosyltransferase (transferase B) uses a UDP-galactose donor to convert the H antigen to B antigen. The amino-acid sequences of transferases A and B differ by four residues, of which only two cause a change in enzyme specificity. These residues are Leu/Met266 and Gly/Ala268 in transferases A and B, respectively. Structural studies revealed that the presence of amino acids with bulky side chains (methionine and alanine) in transferase B cause its inability to bind N-acetylgalactosamine. The recessive trait O, in which antigens A and B are not present, is caused by the expression of an incomplete enzyme as a result of a base deletion and a subsequent reading frame change. In addition to the basic ABO gene variants, several alleles are rarely found that may lead to the expression of enzymes with different specificities. In this article the mechanism of the synthesis of A and B antigens, the molecular background of ABO gene variablity, their allelic variants, and possible mechanisms by which they emerge are described.