People with the same blood group have similar risk for various diseases, specifically certain cancers, cardiovascular disease, and increased susceptibility and more adverse outcome to some infectious/communicable diseases.
Blood group is typically defined by presence or absence of certain antigens on the surface of RBCs (). Of the ~35 different current blood group systems, the , the focus of this answer, is considered the most important (see below from , , ), especially for transfusion medicine.
Ironies About The Human ABO Blood Group System
- Though discovered them all the way back in 1900, hardly anything is known about their function.
- However, function they must have not only because that’s nature’s way but also because they are widely expressed, in endodermal origin tissues of more ancient species such as amphibians and reptiles while also being expressed in ecto- and mesodermal tissues of more recently evolved species such as rodents and primates. Thus they’re expressed on epithelium, sensory neurons, platelets and blood vessels.
- Ironically for molecules whose imprint on the public imagination is precisely their blood cell expression and ensuing need to match blood types during transfusion, their expression on human RBCs is an exception (see below from 4, 5).
Human Global ABO Distribution ()
- O is most common globally.
- A is mainly found in North and Central Europe, rarer in Asia.
- B is quite frequent in Central Asia but almost absent among Amerindians, who are almost exclusively O.
- Clearly, the ABO blood group system exemplifies the fact that human blood group antigens are under active, intensive evolutionary selection pressure.
Human ABO Blood Group System & Disease Risk
- Almost on the heels of the 1900 ABO blood group discovery, people started trotting out associations of different blood types with various human traits, ranging from personality to appropriate diets, the so-called blood group diet being merely one of the latest such fads. Thus far, being scientifically unsubstantiated is the only clear trait linking such tall claims (7).
- OTOH, for many decades little research was done on differential risk for many diseases with different blood groups but in recent years a steady drip of data supporting such associations has emerged.
- ABO blood groups appear to influence susceptibility to pancreatic and gastric cancers, cardiovascular disease and some infectious/communicable diseases (8; see below from 9) with type O tending to have lower risk.
- Several recent epidemiological studies ( , , , , ) suggest O blood type has lower risk of pancreatic cancer.
- Since 1953 ( ), epidemiological studies ( , ) have found blood type A has increased risk of gastric cancer.
- Confirmed by 3 (18, 19, 20), non-O blood types have increased risk of VTE ( ), apparently because circulating is studded with ABH structures in A, B and AB blood types, which in turn increases thrombotic (clotting) risk (see below from ).
- OTOH, type O tends to have substantially lower levels of circulating von Willebrand factor, which further reduces clotting risk.
- Increased VTE risk is especially well-documented for non-O blood types ( , , 23).
- O blood type also has less risk of IS ( ), MI ( ) and PAD ( ) (24).
- The specific O sub-type, O Lewis b, is associated with
- triggered-peptic ulcer, apparently because certain H. pylori strains can bind O lewis b antigen much more strongly compared to A lewis b ).
- Type O are also more susceptible to severe infections with Vibrio cholerae and Escherichia coli (8), and to norovirus-associated acute gastroenteritis ( ).
- OTOH, type O blood has better outcome and less severe symptoms from malaria, which provides a compelling example of microbial selection pressure on evolution of blood group antigens ( ; see below from 28, 29). Protective, i.e., less severe, outcome for type O has been shown both experimentally ( ) as well as through GWAS ( ) ( , 32).
Type O may do better because malaria-infected RBCs express novel proteins such as PfEMP-1 on their surface. In turn, in those with type A or B, such molecules can bind A and B antigens on platelets and blood vessels, setting off an aggregation cascade (see below from).
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