Anti-B antibodies are hypothesized to originate from antibodies produced against Gram-negative bacteria, such as E. coli, cross-reacting with the α-D-galactose on the B glycoprotein.However, it is more likely that the force driving evolution of allele diversity is simply negative frequency-dependent selection; cells with rare variants of membrane antigens are more easily distinguished by the immune system from pathogens carrying antigens from other hosts. Thus, individuals possessing rare types are better equipped to detect pathogens. The high within-population diversity observed in human populations would, then, be a consequence of natural selection on individuals. Clinical relevance
The carbohydrate molecules on the surfaces of red blood cells have roles in cell membrane integrity, cell adhesion, membrane transportation of molecules, and acting as receptors for extracellular ligands, and enzymes. ABO antigens are found having similar roles on epithelial cells as well as red blood cells. Bleeding and thrombosis (von Willebrand factor)
The ABO antigen is also expressed on the von Willebrand factor (vWF) glycoprotein, which participates in hemostasis (control of bleeding). In fact, having type O blood predisposes to bleeding, as 30% of the total genetic variation observed in plasma vWF is explained by the effect of the ABO blood group, and individuals with group O blood normally have significantly lower plasma levels of vWF (and Factor VIII) than do non-O individuals.
Several studies have observed that a relative down-regulation of GTA and GTB occurs in oral carcinomas in association with tumor development. More recently, a genome wide association study (GWAS) has identified variants in the ABO locus associated with susceptibility to pancreatic cancer. In addition, another large GWAS study has associated ABO-histo blood groups as well as FUT2 secretor status with the presence in the intestinal microbiome of specific bacterial species. In this case the association was with Bacteroides and Faecalibacterium spp. Bacteroides of the same OTU (operational taxonomic unit) have been shown to be associated with inflammatory bowel disease, thus the study suggests an important role for the ABO histo-blood group antigens as candidates for direct modulation of the human microbiome in health and disease. Clinical marker
A multi-locus genetic risk score study based on a combination of 27 loci, including the ABO gene, identified individuals at increased risk for both incident and recurrent coronary artery disease events, as well as an enhanced clinical benefit from statin therapy. The study was based on a community cohort study (the Malmo Diet and Cancer study) and four additional randomized controlled trials of primary prevention cohorts (JUPITER and ASCOT) and secondary prevention cohorts (CARE and PROVE IT-TIMI 22). Alteration of ABO antigens for transfusion
In April 2007, an international team of researchers announced in the journal Nature Biotechnology an inexpensive and efficient way to convert types A, B, and AB blood into type O.