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Title: Transcription profiling in human platelets reveals LRRFIP1 as a novel protein regulating platelet function.
Authors: Goodall, AH
Burns, P
Salles, I
Macaulay, IC
Jones, CI
Ardissino, D
de Bono B
Bray, SL
Deckmyn, H
Dudbridge, F
Fitzgerald, DJ
Garner, SF
Gusnanto, A
Koch, K
Langford, C
O'Connor, MN
Rice, CM
Stemple, D
Stephens, J
Trip, MD
Zwaginga, JJ
Samani, NJ
Watkins, NA
Maguire, PB
Ouwehand, WH
Bloodomics, Consortium
First Published: 25-Nov-2010
Citation: BLOOD, 2010, 116 (22), pp. 4646-4656
Abstract: 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, cross-linked 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 hypo thesis for LRRFIP1 [leucine-rich 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.
DOI Link: 10.1182/blood-2010-04-280925
eISSN: 1528-0020
Type: Journal Article
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

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