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

Lanxin Li, Si Cheng, Weina Jin, Hongqiu Gu, Xia Meng, Yong Jiang, Zhe Xu, Yongjun Wang, Hao Li, Jie Zhang, Yang Liu, Lan Gou, Haowen Li, Yingyu Jiang, Yanfeng Shi, Zhenjuan Fang

Journal: Lipids in health and disease 2024;23(1):211

PMID: 38965603

Free Full Text on BioMed Central View on PubMed

Abstract

BACKGROUND

Previous research on ABO blood types and stroke has been controversial, predominantly suggesting heightened risk of stroke in non-O blood types. Nonetheless, investigations into the correlation and underlying mechanisms between ABO blood groups and stroke subtypes, especially within Chinese cohorts, remain limited.

METHODS

The ABO blood types of 9,542 ischaemic stroke (IS) patients were inferred using two ABO gene loci (c.261G > del; c.802G > A). The healthy population was derived from the 1000 Genomes Project. Patients were classified by the causative classification system (CCS). Volcano plot and gene ontology (GO) analysis were employed to explore protein differential expression among blood types. Additionally, HT29 and SW480 cell lines with downregulated ABO expression were generated to evaluate its impact on cholesterol uptake and efflux.

RESULTS

A greater proportion of stroke patients had non-O blood types (70.46%) than did healthy individuals (61.54%). Notable differences in blood type distributions were observed among stroke subtypes, with non-O blood type patients mainly classified as having large artery atherosclerosis (LAA). Clinical baseline characteristics, such as the low-density lipoprotein cholesterol level, activated partial thromboplastin time and thrombin time, varied significantly among blood types. A volcano plot revealed 17 upregulated and 42 downregulated proteins in the O blood type. GO term analysis indicated that downregulated proteins were primarily associated with lipid metabolism pathways. In vitro experiments revealed that reducing ABO gene expression decreased cholesterol uptake and increased cholesterol efflux.

CONCLUSIONS

This study revealed that the non-O blood type increased the risk of LAA stroke through cholesterol metabolism.

Address: Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.; China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.; China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.; China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.; Center of excellence for Omics Research (CORe), Beijing Tiantan Hospital, Capital Medical University, Beijing, China.; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.; Changping Laboratory, Beijing, China.; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. [email protected].; China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. [email protected].; Center of excellence for Omics Research (CORe), Beijing Tiantan Hospital, Capital Medical University, Beijing, China. [email protected].; Changping Laboratory, Beijing, China. [email protected].; Clinical Center for Precision Medicine in Stroke, Capital Medical University, Beijing, China. [email protected].; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. [email protected].; China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. [email protected].; Center of excellence for Omics Research (CORe), Beijing Tiantan Hospital, Capital Medical University, Beijing, China. [email protected].; Changping Laboratory, Beijing, China. [email protected].; Clinical Center for Precision Medicine in Stroke, Capital Medical University, Beijing, China. [email protected].

DOI: 10.1186/s12944-024-02199-6

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MeSH Terms: Humans, ABO Blood-Group System, Male, Cholesterol, Female, Middle Aged, Atherosclerosis, Aged, Stroke, Risk Factors, Cholesterol, LDL, HT29 Cells