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Association of ABO Blood groups and some diseases–Do Blood groups play a biological role?

Francis Ajeneye*

Pathology Department, Blood Transfusion Maidstone and Tunbridge Well Hospitals NHS Trust, TN2 4QJ, U.K

Oladimeji Olofin

Pathology Department, Haematology Maidstone and Tunbridge Well Hospitals NHS Trust, TN2 4QJ, U.K

Christy Chinyere Fredrick

College of Health sciences, Department of Pathology, University of Abuja, Nigeria All correspondence to: Francis Ajeneye f.ajeneye1@nhs.net


The link between ABO/Rh and various diseases have generated much interest over the last decades and have shown some inconsistency. Some diseases are definitely associated with ABO. Do blood groups have biological roles? Many literatures had documented an

association between blood groups and diseases, particularly some neoplasm and hematologic disorders. The loss of blood group A and B antigen expression had been widely documented, which is beyond the scope of this communique. There are also awareness in defining bacterial and parasitic receptors which are closely associated to some known blood groups. Finally, recent studies had observed statistical relationship of blood group with SARS-CoV-2, the association with blood group and SARS-CoV-2 remains insubstantial and evidence must be approached with a sound research design.

Key words: Blood group SARS-CoV-2 Malaria Carcinoma

Over the past few years ABO association with diseases had been widely discussed with emerging research on ABO association and diet, personality and socio-economic statues which is beyond the scope of this short communication.(1,2) Few literatures had proving evidence of increase of group A compared to group with some types of cancer. (3) There is convincing study relating to cancer of the stomach, the association more common in blood group A compared to blood group O. More research across the world agreed with the incidence. ABO association with carcinoma of the stomach seem indisputable(3). Similar association had been also be found in cancer of the colon, and the salivary gland(5). The risk of chorioncarcinoma is critical related to the ABO Blood group of the woman and the partner, women of blood group A with a partner of group O seem to have a highest risk whereas women of blood group A with a partner of blood group A has the lowest risk. There have been some proven relationship of early abortion due to anti-P, Anti-P1 and anti-Pk. The anti-P had been shown to be present in the placenta and anti-PP1PK had been shown to be cytotoxic. (4)

Aird and Bentall (5, 6) showed that group O were 20% more likely to develop peptic ulcer than blood group A. There appears to be a true association between ulceration and absence of secretion. It is not surprising that large quantity of ABH substance are found in the gastrointestinal mucosa,

expression well demonstrated in some human malignancies, the loss of A and B antigen expression was found in 21 of 25 oral carcinoma tumour and correlate with tumour lacking A and B gene expression(7)

There appears to be an association with blood group A, thrombosis, high cholesterol and myocardial infarction. Mourant and colleagues.(8) analysed data from the world literature that patient with thromboembolic diseases include a raised proportion of group A . This applied to women taking oral contraceptive, to pregnancy and puerperal women. There is more evidence of raised thromboembolic episodes in A women than O women. Five year studies found out that A1,B and A1B had a high incidence of myocardial Infarction than O blood group.(9) It was suggested that the etiological pathway of cardiovascular diseases may be differ in patients of different ABO groups owing to difference in their rheology and plasma protein activities.(10,11) These studies consisted of Western Europeans ethnic background, the association did not hold for Asian, African-American or children. It has been shown that cholesterol association may be differ by race.

Mourant(5) made a challenging point earlier that blood

group A individual have a higher level of Factor VIII than group O individual. Group O tend to haemorhage rather than thrombose into the arterial walls thus sustaining more tissue damage. There have also been association with other

failure to secrete ABH substance may lead to peptic ulcer.

coagulation factors such vWF, FV and FIX.(12) Many

There is substantial evidence of decrease activity of glycosyltransferases activities with loss of A and B gene

bacteria such as gram negative organism like Escherichia Coli, have known to have chemical moieties on their

surface that mimics blood group antigens. Springer tested vitro Rosette had been described by to be stronger in

bacteria and found that some bacteria strains showed A, B Group A individuals.(17) The main antigenic ligands

and H (O) specificity.(13) Most blood group scientists responsible for both cytoadherence and antigenic

believe that a similar mechanism must operate in human for the production of naturally occurring antibodies. Small pox virus possess an antigen similar to A antigen, humoral resistance may be more effective in patient with blood group B and O who possess anti-A in their plasma.

The Asian and African distribution of A gene supports the theory of a selective disadvantage among individual infected with smallpox virus. In area like China, India, parts of Russia has a relative increase of the B gene. Resistance to several bacterial and viral infection has been associated with blood groups. Patient with Cholera were likely to be of group O and a one-ninth as likely to be a group AB, several other groups have reported similar associations. (14)

The association of malaria and Duffy blood group system was described by Miller(15), red cell lacking Fya and Fyb were shown to be resistant to the invasion of malaria. It has been shown that black people are resistant to infection by P.Vivax. P.Vivax infection do not occur in individual with Fy(a-b-). The ligand for P. Falciparum is different from the P.Vivax. P.Falciparum invades Fy(a-b-) equally to Fy(a+b+). The parasites exploits adhesion ligands on the endothelial (CD36 and ICAM1), red cell rosette (Blood group A and B), CR1/CD35 and platelets rosettes – platelets glycophorin IV (Cd36) (16) CD36 negative group O appears to be common in malaria endemic areas, this might be a co-incidence or a product of malaria selection, there is also a reduced cyto-adhesion in group O individuals. In-

variation are the members of the P. Falciparum Erythrocyte Membrane Protein-1 (PfEMP1). The encoded PfEMP1var2 carries a two-cysteine-signature associated with rosetting and antibodies to the protein avidly stain the pRBC suggesting that FCR3S1.2 var 2 is the dominant var gene expressed in this parasite.(18)

The parasite ligand-host receptor interactions that mediate cytoadherence is therefore critical to improving our understanding of malaria pathogenesis and developing a vaccine to alleviate disease severity. The second mechanism is to evade specific immune responses through antigenic variation. This involves switching the clonal expression of PfEMP1 antigens, by enabling iRBCs to navigate clear of immunoglobulin (IgG) responses that prevent their cyto-adherence and opsonize them for phagocytosis. PfEMP1 variants thus play a critical role in parasite survival and are prime targets for naturally acquired immunity in African children. Repeating this immunity through PfEMP1 vaccination has been difficult to co-ordinate, especially as thousands of diverse.

There have been other reports associated blood groups with Covid-19, the association of Covid-19 infection and blood groups remains intangible and must be approach with vigilance. The research designs and methodologies identified in recent literatures are not robust and

Cite as: Francis Ajeneye*, Oladimeji Olofin & Christy Chinyere Fredrick (2021). Association of ABO Blood groups and some diseases – Do Blood groups play a biological role?

convincing. A detailed research design that identifies dependent and independent variables and adjust for confounding factors could be a way forward. However, Covid-19 infection could be the results of complex interactions of factors that could vary from genetics, behavioural, metabolic, psychological, social status and environmental risk factors, ABO blood type distribution worldwide varies considerably in different races and should be addressed in studies. In addition to inflammatory response associated with Covid-19 infection,(19) we cannot alterations of the blood group ABO gene in oral overlook mechanism purported by earlier studies that suggested ABO blood group profound influence on the haemostasis, a major determinant of plasma levels of Von

squamous cell carcinoma. Int J Cancer. 2004 Mar 20; 109(2):230-7. doi: 10.1002/ijc.11592. PMID:


Willebrand Factor (VWF).(20,21) Literatures also defined

blood group O as a risk factor for increased severe bleeding while blood group non-O is a risk factor for thromboembolic events. The risk of VTE is probably related to the level of VWF and factor VIII in non-group O subjects. A, B, and H blood group antigens are expressed on N-glycans of vWF and influence the half-life of the protein (10 hours for group O and 25 hours for non-O subjects).


The relationship between ABO blood groups and overall cancer risk still remains unclear but several meta-analyses conducted over decades suggested there is a strong link. The geographic distribution of ABO antigens worldwide is consistent with a survival advantage in malaria among group O individuals; clinical studies had provided supporting evidence of the effect of ABO group on malaria severity; and that recent discoveries suggest biologic mechanisms linking disease pathogenesis to ABO antigen expression. The mechanisms underlying the associations between ABO blood group and Cardiovascular diseases risk remain unclear, however, several studies of evidence support its potential cardiovascular effects. More research is required to explore and understand the association of Blood groups and SARS-CoV-2.

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