The ABO blood group system is one of the most clinically significant human blood‑group systems and has been implicated in the pathogenesis, progression, and prognosis of multiple diseases. This narrative review synthesizes recent epidemiological evidence and explores potential mechanisms connecting ABO blood type to cardiovascular diseases, malignancies, diabetes, Plasmodium falciparum malaria, COVID‑19, and rheumatic diseases.
The authors performed a literature search of PubMed and CNKI through September 2025. The review is narrative in design and integrates epidemiological findings and mechanistic hypotheses reported in the identified studies. Specific study selection criteria, search strings, and quantitative meta‑analytic methods (beyond pooled estimates referred to in the abstract) were not detailed in the abstract.
Epidemiological studies summarized in the review consistently report that individuals with non‑O blood groups (A, B, AB) have an elevated risk of cardiovascular events compared with group O. A prominent and repeatedly observed signal is the association with thrombotic outcomes: risk of venous thromboembolism (VTE) in non‑O groups is reported to be roughly two‑ to fourfold higher than in those with blood group O. The review frames these associations as robust across multiple studies but does not assert causality; it notes the need to further investigate mediating biological pathways.
The review reports that ABO blood group influences both susceptibility to certain cancers and clinical prognosis. The most frequently cited example is an association between blood group A and increased risk of gastric cancer; a pooled odds ratio of approximately 1.2 is noted. Other cancer types and prognostic links are discussed in the full review, but the abstract highlights that ABO status can modulate both incidence and outcomes in oncology cohorts.
ABO associations with diabetes are discussed as part of the review’s scope. The abstract indicates that ABO genetic variation has been investigated in relation to diabetes epidemiology and genetics. Specific effect sizes or consistent directional associations for diabetes were not presented in the abstract; the review characterizes this area as one of several disease domains where ABO may influence susceptibility or phenotype.
A consistent epidemiological finding summarized in the review is that individuals with blood group O exhibit relative resistance to severe falciparum malaria compared with non‑O groups. This protective association for group O in the context of severe malaria is noted as a recurrent observation in malaria research and is included among the key disease links for ABO.
During the COVID‑19 pandemic, multiple studies examined associations between ABO blood type and SARS‑CoV‑2 infection risk and disease severity. The review indicates that blood group A was linked to higher susceptibility and greater severity in some datasets, whereas blood group O appeared to offer mild protection. Importantly, these associations displayed substantial heterogeneity across geographic populations, viral variants, and vaccination contexts, and therefore cannot be generalized without caution.
The review notes that ABO polymorphisms may modulate risk and clinical manifestations of rheumatic diseases such as systemic lupus erythematosus and rheumatoid arthritis. The evidence is presented as suggestive rather than definitive, indicating that ABO loci could be one of multiple genetic contributors to rheumatic disease susceptibility and phenotype.
The authors discuss potential biological mechanisms that might underlie observed epidemiological associations, including genetic linkage, modulation of coagulation and thrombosis pathways, interactions with pathogens, and effects on inflammation and immune responses. Specific mechanistic pathways are not exhaustively detailed in the abstract, and the review frames many of these concepts as hypotheses requiring further experimental and clinical validation.
The review emphasizes that current evidence is largely hypothesis‑generating. While associations between ABO status and several disease outcomes are reproducible in many contexts, causal inference is not established. The authors highlight the potential of ABO typing as a candidate biomarker for risk stratification in precision medicine but stress that robust validation is required. They call for large, multi‑ethnic prospective studies to clarify causal mechanisms and to test the predictive utility of ABO status across diverse populations and clinical settings.
Accumulating epidemiological and mechanistic evidence links ABO blood groups to susceptibility and outcomes across a range of diseases, notably cardiovascular disease, cancer, malaria, and COVID‑19, with additional suggestive links to diabetes and rheumatic diseases. The review concludes these findings generate hypotheses for further research rather than immediate clinical practice change. Large, prospective, multi‑ethnic studies are needed to confirm causality and to evaluate whether ABO typing can be translated into validated risk‑stratification tools.