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表达表型决定血小板和血管性血友病因子上的 ABO(H)血型抗原的加载。

Expresser phenotype determines ABO(H) blood group antigen loading on platelets and von Willebrand factor.

机构信息

Irish Blood Transfusion Service, Dublin, Ireland.

Department of Haematology, Trinity College Dublin, Dublin, Ireland.

出版信息

Sci Rep. 2020 Oct 27;10(1):18366. doi: 10.1038/s41598-020-75462-2.

DOI:10.1038/s41598-020-75462-2
PMID:33110150
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7591562/
Abstract

ABO blood group is associated with cardiovascular disease, with significantly lower risk in blood group O individuals. ABO(H) blood group determinants are expressed on different glycoproteins on platelet surfaces. In addition, ABO(H) structures are also present on VWF glycans. These ABO(H) carbohydrates influence both platelet and VWF function. Previous studies have reported that approximately 5-10% of normal blood donors express abnormally high or low levels of A or B blood group antigens on their platelet surfaces (high expresser phenotype, HXP or low expresser phenotype, LXP respectively). In this study, the biological effects of the ABO Expresser phenotype were investigated. ABO(H) expression on platelets and plasma VWF was studied in a series of 541 healthy blood donors. Overall, 5.6% of our study cohort were classified as HXP, whilst 4.4% satisfied criteria for LXP. We demonstrate that genotype at the ABO blood group locus plays a critical role in modulating the platelet HXP phenotype. In particular, AA genotype is a major determinant of ABO high-expresser trait. Our data further show that ABH loading on VWF is also affected by ABO expresser phenotype. Consequently, A antigen expression on VWF was significantly elevated in HXP individuals and moderately reduced in LXP subjects (P < 0.05). Collectively, these findings suggest that ABO expresser phenotype influences primary hemostasis though several different pathways. Further studies will be required to define whether inter-individual variations in ABO(H) expression on platelets and/or VWF (particularly HXP and LXP) impact upon risk for cardiovascular disease.

摘要

ABO 血型与心血管疾病相关,O 型血个体的风险显著降低。ABO(H)血型决定簇表达在血小板表面的不同糖蛋白上。此外,ABO(H)结构也存在于 VWF 聚糖上。这些 ABO(H)碳水化合物会影响血小板和 VWF 的功能。先前的研究报告称,大约 5-10%的正常献血者在其血小板表面表达异常高水平或低水平的 A 或 B 血型抗原(分别为高表达表型,HXP 或低表达表型,LXP)。在这项研究中,研究了 ABO 表达者表型的生物学效应。在一系列 541 名健康献血者中,研究了 ABO(H)在血小板和血浆 VWF 上的表达。总体而言,我们研究队列中有 5.6%的人被归类为 HXP,而 4.4%的人符合 LXP 的标准。我们证明 ABO 血型基因座上的基因型在调节血小板 HXP 表型方面起着关键作用。特别是,AA 基因型是 ABO 高表达特征的主要决定因素。我们的数据进一步表明,ABH 在 VWF 上的加载也受到 ABO 表达者表型的影响。因此,HXP 个体的 VWF 上 A 抗原表达显著升高,而 LXP 个体的 VWF 上 A 抗原表达适度降低(P<0.05)。总的来说,这些发现表明 ABO 表达者表型通过几种不同的途径影响主要止血。需要进一步的研究来确定血小板和/或 VWF 上 ABO(H)表达的个体差异(特别是 HXP 和 LXP)是否会影响心血管疾病的风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67bd/7591562/5d1cabb25662/41598_2020_75462_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67bd/7591562/5dfcd2ce4918/41598_2020_75462_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67bd/7591562/5dfcd2ce4918/41598_2020_75462_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67bd/7591562/3846c54d27d4/41598_2020_75462_Fig2_HTML.jpg
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