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



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.



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 < 0.0125). More modest associations were observed between A1 allele dosage and levels of sICAM-1, with ABO alleles explaining 0.8-1.1% of the total phenotypic variation within race/ethnicity. ABO associations with vWF activity were consistent across race/ethnicity, with B allele carriers corresponding to the highest vWF activity levels.



ABO blood type demonstrates complex associations with endothelial markers that are largely generalizable across diverse populations.
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA. Electronic address: Larson.nicholas@mayo.edu.
Nicholas B
NB
Larson
Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
Elizabeth J
EJ
Bell
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
Paul A
PA
Decker
Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
Mindy
M
Pike
Department of Pathology and Laboratory Medicine, University of Vermont, Burlington, VT, USA.
Christina L
CL
Wassel
Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
Michael Y
MY
Tsai
Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
James S
JS
Pankow
Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
Weihong
W
Tang
Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
Naomi Q
NQ
Hanson
Department of Pathology and Laboratory Medicine, University of Vermont, Burlington, VT, USA; Department of Medicine, University of Vermont, Burlington, VT, USA.
Kristine
K
Alexander
Department of Pathology and Laboratory Medicine, University of Vermont, Burlington, VT, USA; Department of Medicine, University of Vermont, Burlington, VT, USA.
Neil A
NA
Zakai
Department of Pathology and Laboratory Medicine, University of Vermont, Burlington, VT, USA; Department of Medicine, University of Vermont, Burlington, VT, USA.
Mary
M
Cushman
Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
Suzette J
SJ
Bielinski
D000017:ABO Blood-Group System; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D050197:Atherosclerosis / Q000097:blood* / Q000208:ethnology / Q000235:genetics*; D002448:Cell Adhesion; D019040:E-Selectin / Q000097:blood / Q000235:genetics; D004730:Endothelium, Vascular / Q000473:pathology*; D005006:Ethnicity; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000235:genetics; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood / Q000235:genetics; D011110:Polymorphism, Genetic; D014841:von Willebrand Factor / Q000235:genetics / Q000378:metabolism
D000017:ABO Blood-Group System; D019040:E-Selectin; D019007:P-Selectin; C546936:SELE protein, human; C546937:SELP protein, human; D014841:von Willebrand Factor; D018799:Intercellular Adhesion Molecule-1
ABO; Cellular adhesion; Multi-ethnic; Von willebrand factor