ABO blood group associations with markers of endothelial dysfunction in the Multi-Ethnic Study of Atherosclerosis

Abstract Background and aims ABO blood type is associated with cardiovascular disease, although the underlying mechanisms are presumed to be complex. While the relationship between non-O blood types and von Willebrand Factor (vWF) is well-established, associations with cellular adhesion molecules (CAMs) across diverse populations are understudied. Methods We genetically inferred ABO alleles for N = 6202 participants from the Multi-Ethnic Study of Atherosclerosis. Linear regression was used to evaluate associations between major ABO allele dosages and log-transformed measurements of vWF (N = 924), soluble E-selectin (sE-selectin, N = 925), soluble P-selectin (sP-selectin, N = 2392), and soluble ICAM-1 (sICAM-1, N = 2236) by race/ethnicity. Results For the selectins, the A1 allele was associated with significantly lower levels for all races/ethnicities, with each additional allele resulting in a 28–39% decrease in sE-selectin and 10–18% decrease in sP-selectin relative to Type O subjects. However, the A2 allele demonstrated effect heterogeneity across race/ethnicity for sE-selectin, with lower levels for non-Hispanic whites ( p  = 0.0011) but higher levels for Hispanics ( p  = 0.0021). We also identified elevated sP-selectin levels for B-allele carriers solely in Hispanic participants ( p  = 1.0E-04). ABO-by-race/ethnicity interactions were significant for both selectins ( p Conclusions ABO blood type demonstrates complex associations with endothelial markers that are largely generalizable across diverse populations.