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Blood, 1 October 2005, Vol. 106, No. 7, pp. 2356-2362. Prepublished online as a Blood First Edition Paper on June 14, 2005; DOI 10.1182/blood-2005-02-0723. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: 2005-02-0723v1 106/7/2356    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Freson, K. Articles by Van Geet, C. Search for Related Content PubMed PubMed Citation Articles by Freson, K. Articles by Van Geet, C. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 23, 2005 Accepted June 5, 2005 The 1-tubulin Q43P functional polymorphism reduces the risk of cardiovascular disease in men by modulating platelet function and structure Kathleen Freson*, Rita De Vos, Christine Wittevrongel, Chantal Thys, Johan Defoor, Luc Vanhees, Jos Vermylen, Kathelijne Peerlinck, and Chris Van Geet Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium Department of Pathology, University of Leuven, Leuven, Belgium Cardiovascular Rehabilitation Unit, Dept. of Rehabilitation Sciences, Faculty of Physical Education and Physical Therapy, University of Leuven, Leuven, Belgium Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium; Department of Pediatrics, University of Leuven, Leuven, Belgium * Corresponding author; email: kathleen.freson{at}med.kuleuven.ac.be. The discoid form of platelets is maintained by a marginal band of tightly coiled microtubules. 1-tubulin is the major isoform within platelet and megakaryocyte microtubules. In 24.2 % of 33 unrelated inherited macrothrombocytopenia patients and in 10.6 % of 272 subjects of a normal population a Pro for Gln substitution in 1-tubulin was found in the highly conserved residue 43. Heterozygous carriers of the Q43P variant showed a reduced platelet protein 1-tubulin expression. Transfection of green fluorescent protein (GFP)-tagged Q43P 1-tubulin in megakaryocytic MEG01 cells resulted in a disturbed tubulin organization. Electron microscopy revealed enlarged spherocytic platelets with a disturbed marginal band and organelle-free zones. In addition, platelets with the Q43P 1-tubulin variant had reduced ATP secretion, TRAP-induced aggregation and collagen adhesion. The prevalence of the Q43P 1-tubulin variant was also 2 times higher (OR= 2.1, 95% CI 1.22-3.59) among control subjects than among patients with cardiovascular disease (10.4 % versus 5.2 %, P = .0082). By analysing this protective factor in men and women separately, this association was only found in men. This study thus presents the functional consequences of the platelet Q43P 1-tubulin substitution that is frequent in the normal population and may protect men against arterial thrombosis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: 1-tubulin in human platelets: not simply a structural cell frame Paolo Gresele and Emanuela Falcinelli Blood 2005 106: 2229-2230. [Full Text] [PDF] This article has been cited by other articles: S. Kunishima, R. Kobayashi, T. J. Itoh, M. Hamaguchi, and H. Saito Mutation of the {beta}1-tubulin gene associated with congenital macrothrombocytopenia affecting microtubule assembly Blood, January 8, 2009; 113(2): 458 - 461. [Abstract] [Full Text] [PDF] L. Navarro-Nunez, M. L. Lozano, J. Rivera, J. Corral, V. Roldan, R. Gonzalez-Conejero, J. A. Iniesta, J. Montaner, V. Vicente, and C. Martinez The association of the {beta}1-tubulin Q43P polymorphism with intracerebral hemorrhage in men Haematologica, April 1, 2007; 92(4): 513 - 518. [Abstract] [Full Text] [PDF]

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