Title: Transcription profiling in human platelets reveals LRRFIP1 as a novel protein regulating platelet function
Authors: Goodall, Alison H ×
Burns, Philippa
Salles, Isabelle
Macaulay, Iain C
Jones, Chris I
Ardissino, Diego
de Bono, Bernard
Bray, Sarah L
Deckmyn, Hans
Dudbridge, Frank
Fitzgerald, Desmond J
Garner, Stephen F
Gusnanto, Arief
Koch, Kerstin
Langford, Cordelia
O'Connor, Marie N
Rice, Catherine M
Stemple, Derek
Stephens, Jonathan
Trip, Mieke D
Zwaginga, Jaap-Jan
Samani, Nilesh J
Watkins, Nicholas A
Maguire, Patricia B
Ouwehand, Willem H #
Issue Date: Nov-2010
Publisher: W.B. Saunders
Series Title: Blood vol:116 issue:22 pages:4646-4656
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.
ISSN: 0006-4971
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Interdisciplinary Research Facility Life Sciences, Campus Kulak Kortrijk
Chemistry, Campus Kulak Kortrijk
× corresponding author
# (joint) last author

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