Transcription profiling in human platelets reveals LRRFIP1 as a novel protein regulating platelet function

被引：73

作者：

Goodall, Alison H. ^{[1
,2
]}

Burns, Philippa ^{[3
,5
]}

Salles, Isabelle ^{[4
,6
]}

Macaulay, Iain C. ^{[7
]}

Jones, Chris I. ^{[1
]}

Ardissino, Diego ^{[8
]}

de Bono, Bernard ^{[9
]}

Bray, Sarah L. ^{[10
]}

Deckmyn, Hans ^{[4
]}

Dudbridge, Frank ^{[10
]}

Fitzgerald, Desmond J. ^{[7
]}

Garner, Stephen F. ^{[3
,5
]}

Gusnanto, Arief ^{[10
]}

Koch, Kerstin ^{[3
,5
]}

Langford, Cordelia ^{[6
]}

O'Connor, Marie N. ^{[3
,5
,6
]}

Rice, Catherine M. ^{[6
]}

Stemple, Derek ^{[6
]}

Stephens, Jonathan ^{[3
,5
]}

Trip, Mieke D. ^{[11
]}

Zwaginga, Jaap-Jan ^{[12
]}

Samani, Nilesh J. ^{[1
,2
]}

Watkins, Nicholas A. ^{[3
,5
]}

Maguire, Patricia B. ^{[7
]}

Ouwehand, Willem H. ^{[3
,5
]}

机构：

[1] Univ Leicester, Dept Cardiovasc Sci, Glenfield Hosp, Leicester LE3 9QP, Leics, England

[2] Glenfield Hosp, Leicester NIHR Biomed Res Unit Cardiovasc Dis, Leicester, Leics, England

[3] Univ Cambridge, Dept Hematol, Cambridge, England

[4] IRC KU Leuven, Lab Thrombosis Res, Kortrijk, Belgium

[5] Natl Hlth Serv Blood & Transplant, Cambridge, England

[6] Wellcome Trust Sanger Inst, Cambridge, England

[7] Univ Coll Dublin Belfield, Sch Biomol & Biomed Sci, UCD Conway Inst, Dublin, Ireland

[8] Univ Parma, Div Cardiol, Osped Maggiore, Assoc Studio Trombosi Cardiol, I-43100 Parma, Italy

[9] European Bioinformat Inst, Cambridge, England

[10] MRC, Biostat Unit, Cambridge CB2 2BW, England

[11] Sanquin Blood Supply Fdn, Amsterdam, Netherlands

[12] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands

来源：

BLOOD | 2010年 / 116卷 / 22期

关键词：

LEUCINE-RICH REPEAT; GENE-EXPRESSION; FLIGHTLESS-I; IDENTIFICATION; AGGREGATION; LOCI; MEGAKARYOCYTES; GENOMICS; VARIANT; FAMILY;

D O I：

10.1182/blood-2010-04-280925

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Within the healthy population, there is substantial, heritable, and interindividual variability in the platelet response. We explored whether a proportion of this variability could be accounted for by interindividual variation in gene expression. Through a correlative analysis of genome-wide platelet RNA expression data from 37 subjects representing the normal range of platelet responsiveness within a cohort of 500 subjects, we identified 63 genes in which transcript levels correlated with variation in the platelet response to adenosine diphosphate and/or the collagen-mimetic peptide, crosslinked collagen-related peptide. Many of these encode proteins with no reported function in platelets. An association study of 6 of the 63 genes in 4235 cases and 6379 controls showed a putative association with myocardial infarction for COMMD7 (COMM domain-containing protein 7) and a major deviation from the null hypothesis for LRRFIP1 [leucinerich repeat (in FLII) interacting protein 1]. Morpholino-based silencing in Danio rerio identified a modest role for commd7 and a significant effect for lrrfip1 as positive regulators of thrombus formation. Proteomic analysis of human platelet LRRFIP1-interacting proteins indicated that LRRFIP1 functions as a component of the platelet cytoskeleton, where it interacts with the actin-remodeling proteins Flightless-1 and Drebrin. Taken together, these data reveal novel proteins regulating the platelet response. (Blood. 2010; 116(22): 4646-4656)

引用

页码：4646 / 4656

页数：11

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