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

Goodall, A. H., Burns, P., Salles, I., Macaulay, I. C., Jones, C. I., Ardissino, D., de Bono, B., Bray, S. L., Deckmyn, H., Dudbridge, F., Fitzgerald, D. J., Garner, S. F., Gusnanto, A., Koch, K., Langford, C., O'Connor, M. N., Rice, C. M., Stemple, D., Stephens, J., Trip, M. D. , Zwaginga, J. J., Samani, N. J., Watkins, N. A., Maguire, P. B. and Ouwehand, W. H. (2010) Transcription profiling in human platelets reveals LRRFIP1 as a novel protein regulating platelet function. Blood, 116 (22). pp. 4646-4656. ISSN 0006-4971

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To link to this item DOI: 10.1182/blood-2010-04-280925

Abstract/Summary

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.

Item Type:Article
Refereed:Yes
Divisions:No Reading authors. Back catalogue items
Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR)
Faculty of Life Sciences > School of Biological Sciences > Biomedical Sciences
ID Code:33133
Uncontrolled Keywords:platelets, transcription, genome, GWAS
Publisher:American Society of Hematology

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