ABO Blood Type and Stroke Risk: the REasons for Geographic And Racial Differences in Stroke Study

Overview

Journal J Thromb Haemost

Publisher Elsevier

Specialty Hematology

Date 2014 Jan 22

PMID 24444093

Citations 50

Authors

N A Zakai

S E Judd

K Alexander

L A McClure

B M Kissela

G Howard

M Cushman

Affiliations

Soon will be listed here.

Abstract

Background: ABO blood type is an inherited trait associated with coagulation factor levels and vascular outcomes.

Objectives: To assess the association of blood type with stroke and whether blood type contributes to racial disparities in stroke in the United States.

Patients And Methods: The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study recruited 30 239 participants between 2003 and 2007. Using a case-cohort design, blood type was genotyped in 646 participants with stroke and a 1104-participant cohort random sample. Cox models that adjusted for Framingham stroke risk factors were used to assess the association of blood type with stroke.

Results: During 5.8 years of follow-up, blood types A or B vs. type O were not associated with stroke. Blood type AB vs. O was associated with an increased risk of stroke (adjusted hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.01-3.30). The association of blood type AB vs. O was greater in those without diabetes (adjusted HR 3.33, 95% CI 1.61-6.88) than those with diabetes (adjusted HR 0.49, 95% CI 0.17-1.44) (P interaction = 0.02). Factor VIII levels accounted for 60% (95% CI 11%-98%) of the association of AB blood type and stroke risk.

Conclusion: Blood type AB is associated with an increased risk of stroke that is not attenuated by conventional stroke risk factors, and factor VIII levels were associated with 60% of the association. While blood type AB is rare in the US population, it is a significant stroke risk factor and may play an important role in stroke risk in these individuals.

Citing Articles

Additive association of blood group A allele with 15 cardiometabolic diseases: a UK Biobank life-course study.

Zhao R, Xian W, Ma Y, Napolioni V, Lau P, Tian X Cardiovasc Diabetol. 2025; 24(1):113.

PMID: 40065387 PMC: 11895148. DOI: 10.1186/s12933-025-02669-w.

Targeted Metabolomics in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study.

Ament Z, Kijpaisalratana N, Bhave V, Couch C, Garcia Guarniz A, Patki A Sci Data. 2025; 12(1):395.

PMID: 40050322 PMC: 11885657. DOI: 10.1038/s41597-025-04746-x.

NeuroimaGene: an R package for assessing the neurological correlates of genetically regulated gene expression.

Bledsoe X, Gamazon E BMC Bioinformatics. 2024; 25(1):325.

PMID: 39379815 PMC: 11463069. DOI: 10.1186/s12859-024-05936-x.

Non-O blood types are associated with a greater risk of large artery atherosclerosis stroke and dysregulation of cholesterol metabolism: an observational study.

Gou L, Li H, Jiang Y, Liu Y, Gu H, Xu Z Lipids Health Dis. 2024; 23(1):211.

PMID: 38965603 PMC: 11223365. DOI: 10.1186/s12944-024-02199-6.

The association between ABO blood types and peripherally inserted central catheter-related venous thrombosis for patients with cancer: A retrospective 7-year single-center experience and meta-analysis.

Wu X, Xiao Y, Tian R PLoS One. 2024; 19(7):e0305746.

PMID: 38950056 PMC: 11216569. DOI: 10.1371/journal.pone.0305746.

References

Kulathinal S, Karvanen J, Saarela O, Kuulasmaa K . Case-cohort design in practice - experiences from the MORGAM Project. Epidemiol Perspect Innov. 2007; 4:15. PMC: 2216006. DOI: 10.1186/1742-5573-4-15. View

Ikram M, Seshadri S, Bis J, Fornage M, DeStefano A, Aulchenko Y . Genomewide association studies of stroke. N Engl J Med. 2009; 360(17):1718-28. PMC: 2768348. DOI: 10.1056/NEJMoa0900094. View

Patnaik S, Helmberg W, Blumenfeld O . BGMUT: NCBI dbRBC database of allelic variations of genes encoding antigens of blood group systems. Nucleic Acids Res. 2011; 40(Database issue):D1023-9. PMC: 3245102. DOI: 10.1093/nar/gkr958. View

Demarmels Biasiutti F, Berger D, Mattle H, Lammle B, Wuillemin W . Hemostatic risk factors in ischemic stroke. Thromb Haemost. 2003; 90(6):1094-9. DOI: 10.1160/TH03-03-0134. View

Howard V, Kleindorfer D, Judd S, McClure L, Safford M, Rhodes J . Disparities in stroke incidence contributing to disparities in stroke mortality. Ann Neurol. 2011; 69(4):619-27. PMC: 3595534. DOI: 10.1002/ana.22385. View

He M, Wolpin B, Rexrode K, Manson J, Rimm E, Hu F . ABO blood group and risk of coronary heart disease in two prospective cohort studies. Arterioscler Thromb Vasc Biol. 2012; 32(9):2314-20. PMC: 3488453. DOI: 10.1161/ATVBAHA.112.248757. View

Sarode R, Goldstein J, Sussman I, Nagel R, Tsai H . Role of A and B blood group antigens in the expression of adhesive activity of von Willebrand factor. Br J Haematol. 2000; 109(4):857-64. DOI: 10.1046/j.1365-2141.2000.02113.x. View

Ranade K, Chang M, Ting C, Pei D, Hsiao C, Olivier M . High-throughput genotyping with single nucleotide polymorphisms. Genome Res. 2001; 11(7):1262-8. PMC: 311112. DOI: 10.1101/gr.157801. View

Howard G, Cushman M, Kissela B, Kleindorfer D, McClure L, Safford M . Traditional risk factors as the underlying cause of racial disparities in stroke: lessons from the half-full (empty?) glass. Stroke. 2011; 42(12):3369-75. PMC: 3226886. DOI: 10.1161/STROKEAHA.111.625277. View

10.

Williams F, Carter A, Hysi P, Surdulescu G, Hodgkiss D, Soranzo N . Ischemic stroke is associated with the ABO locus: the EuroCLOT study. Ann Neurol. 2013; 73(1):16-31. PMC: 3582024. DOI: 10.1002/ana.23838. View

11.

Stephens M, Scheet P . Accounting for decay of linkage disequilibrium in haplotype inference and missing-data imputation. Am J Hum Genet. 2005; 76(3):449-62. PMC: 1196397. DOI: 10.1086/428594. View

12.

Yazer M, Hosseini-Maaf B, Olsson M . Blood grouping discrepancies between ABO genotype and phenotype caused by O alleles. Curr Opin Hematol. 2008; 15(6):618-24. DOI: 10.1097/MOH.0b013e3283127062. View

13.

Barlow W, Ichikawa L, ROSNER D, Izumi S . Analysis of case-cohort designs. J Clin Epidemiol. 1999; 52(12):1165-72. DOI: 10.1016/s0895-4356(99)00102-x. View

14.

Zakai N, Katz R, Jenny N, Psaty B, Reiner A, Schwartz S . Inflammation and hemostasis biomarkers and cardiovascular risk in the elderly: the Cardiovascular Health Study. J Thromb Haemost. 2007; 5(6):1128-35. DOI: 10.1111/j.1538-7836.2007.02528.x. View

15.

Pare G, Chasman D, Kellogg M, Zee R, Rifai N, Badola S . Novel association of ABO histo-blood group antigen with soluble ICAM-1: results of a genome-wide association study of 6,578 women. PLoS Genet. 2008; 4(7):e1000118. PMC: 2432033. DOI: 10.1371/journal.pgen.1000118. View

16.

Zhang H, Mooney C, Reilly M . ABO Blood Groups and Cardiovascular Diseases. Int J Vasc Med. 2012; 2012:641917. PMC: 3485501. DOI: 10.1155/2012/641917. View

17.

Stephens M, Smith N, Donnelly P . A new statistical method for haplotype reconstruction from population data. Am J Hum Genet. 2001; 68(4):978-89. PMC: 1275651. DOI: 10.1086/319501. View

18.

Folsom A, Rosamond W, Shahar E, Cooper L, Aleksic N, Nieto F . Prospective study of markers of hemostatic function with risk of ischemic stroke. The Atherosclerosis Risk in Communities (ARIC) Study Investigators. Circulation. 1999; 100(7):736-42. DOI: 10.1161/01.cir.100.7.736. View

19.

Watala C . Hyperglycaemia alters the physico-chemical properties of proteins in erythrocyte membranes of diabetic patients. Int J Biochem. 1992; 24(11):1755-61. DOI: 10.1016/0020-711x(92)90125-k. View

20.

Gailani D, Renne T . Intrinsic pathway of coagulation and arterial thrombosis. Arterioscler Thromb Vasc Biol. 2007; 27(12):2507-13. DOI: 10.1161/ATVBAHA.107.155952. View