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


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; (2010) Transcription profiling in human platelets reveals LRRFIP1 as a novel protein regulating platelet function. Blood. ISSN 0006-4971 DOI: https://doi.org/10.1182/blood-2010-04-280925

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Abstract

Within the normal population there is substantial, heritable, inter-individual variability in the platelet response. We explored whether a proportion of this variability can be accounted for by inter-individual variation in gene expression. Through a correlative analysis of genome-wide platelet RNA expression data from 37 individuals representing the normal range of platelet responsiveness within a cohort of 500 individuals we identified 63 genes where transcript levels were correlated with variation in the platelet response to ADP and/or the collagen-mimetic peptide CRP-XL. Many of these encode proteins with no reported function in platelets. An association study of six of the 63 genes in 4,235 cases and 6,379 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 (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 remodelling proteins Flightless-1 and Drebrin. Taken together these data reveal novel proteins regulating the platelet response.

Item Type: Article
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology
PubMed ID: 20833976
Web of Science ID: 284599900038
URI: http://researchonline.lshtm.ac.uk/id/eprint/2651

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