Aspirin insensitive thrombophilia: Transcript profiling of blood identifies platelet abnormalities and HLA restriction

被引：9

作者：

Fallahi, Payam ^{[1
,3
]}

Katz, Richard ^{[1
,3
]}

Toma, Ian ^{[1
,2
]}

Li, Ranyang ^{[1
,2
]}

Reiner, Jonathan ^{[1
,3
]}

VanHouten, Kiersten ^{[1
,2
]}

Carpio, Larry ^{[1
,2
]}

Marshall, Lorraine ^{[1
,3
]}

Lian, Yi ^{[1
,2
]}

Bupp, Sujata ^{[1
,2
]}

Fu, Sidney W. ^{[1
,2
,5
]}

Rickles, Frederick ^{[1
,4
]}

Leitenberg, David ^{[5
]}

Lai, Yinglei ^{[6
]}

Weksler, Babette B. ^{[7
]}

Rebling, Frederik ^{[1
,2
]}

Yang, Zhaoqing ^{[1
,2
]}

McCaffrey, Timothy A. ^{[1
,2
,5
]}

机构：

[1] George Washington Univ, Med Ctr, Dept Med, Washington, DC 20037 USA

[2] George Washington Univ, Med Ctr, Div Genom Med, Washington, DC 20037 USA

[3] George Washington Univ, Med Ctr, Div Cardiol, Washington, DC 20037 USA

[4] George Washington Univ, Med Ctr, Div Hematol Oncol, Washington, DC 20037 USA

[5] George Washington Univ, Med Ctr, Dept Microbiol Immunol & Trop Med, Washington, DC 20037 USA

[6] George Washington Univ, Med Ctr, Dept Stat, Biostat Ctr, Washington, DC 20037 USA

[7] Weill Cornell Univ, Coll Med, Div Hematol Oncol, Dept Med, New York, NY USA

来源：

GENE | 2013年 / 520卷 / 02期

关键词：

Aspirin; Coagulation; Genetics; Platelets; Thrombosis; Transcript profiling; PRIMARY ANTIPHOSPHOLIPID SYNDROME; HUMAN NEUTROPHIL ELASTASE; ANTIPLATELET THERAPY; GLYCOPROTEIN-IIIA; GENE-EXPRESSION; RESISTANCE; AGGREGATION; DISEASE; METAANALYSIS; ASSOCIATION;

D O I：

10.1016/j.gene.2013.02.032

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Aspirin is the most widely used antiplatelet agent because it is safe, efficient, and inexpensive. However, a significant subset of patients does not exhibit a full inhibition of platelet aggregation, termed 'aspirin resistance' (AR). Several major studies have observed that AR patients have a 4-fold increased risk of myocardial infarction (MI), stroke, and other thrombotic events. Arachidonic acid-stimulated whole blood aggregation was tested in 132 adults at risk for ischemic events, and identified an inadequate response to aspirin therapy in 9 patients (6.8%). Expression profiling of blood RNA by microarray was used to generate new hypotheses about the etiology of AR. Among the differentially expressed genes, there were decreases in several known platelet transcripts, including clusterin (CLU), glycoproteins IIb/IIIa (ITGA2B/3), lipocalin (LCN2), lactoferrin (LTF), and the thrombopoetin receptor (MPL), but with increased mRNA for the T-cell Th1 chemokine CXCL10. There was a strong association of AR with expression of HLA-DRB4 and HLA-DQA1. Similar HLA changes have been linked to autoimmune disorders, particularly antiphospholipid syndrome (APS), in which autoantibodies to phospholipid/protein complexes can trigger platelet activation. Consistent with APS, AR patients exhibited a 30% reduction in platelet counts. Follow-up testing for autoimmune antibodies observed only borderline titers in AR patients. Overall, these results suggest that AR may be related to changes in platelet gene expression creating a hyperreactive platelet, despite antiplatelet therapy. Future studies will focus on determining the protein levels of these differential transcripts in platelets, and the possible involvement of HLA restriction as a contributing factor. (c) 2013 Elsevier B.V. All rights reserved.

引用

页码：131 / 138

页数：8

共 52 条

[1] The platelet protein kinase C substrate pleckstrin binds directly to SDPR protein [J].