Journal
ATHEROSCLEROSIS
Volume 251, Issue -, Pages 422-429Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2016.05.049
Keywords
Cellular adhesion; Von willebrand factor; Multi-ethnic; ABO
Funding
- United States Environmental Protection Agency [RD831697]
- NHLBI [R01HL98077]
- National Heart, Lung, and Blood Institute (NHLBI)
- [N02-HL-64278]
- [HL071205]
- [UL1TR000124]
- [DK063491]
- [P50 ES015915]
- [N01-HC-95159]
- [N01-HC-95160]
- [N01-HC-95161]
- [N01-HC-95162]
- [N01-HC-95163]
- [N01-HC-95164]
- [N01-HC-95165]
- [N01-HC-95166]
- [N01-HC-95167]
- [N01-HC-95168]
- [N01-HC-95169]
- [UL1-TR-001079]
- [UL1-TR-000040]
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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 28e39% 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. Conclusions: ABO blood type demonstrates complex associations with endothelial markers that are largely generalizable across diverse populations. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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