Haematologica
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Haematologica, Vol 92, Issue 4, 513-518 doi:10.3324/haematol.10689
Copyright © 2007 by Ferrata Storti Foundation
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Disorders of Hemostasis

The association of the ß1-tubulin Q43P polymorphism with intracerebral hemorrhage in men

Leyre Navarro-Núñez, María L. Lozano, José Rivera, Javier Corral, Vanessa Roldán, Rocío González-Conejero, Juan A. Iniesta, Joan Montaner, Vicente Vicente, Constantino Martínez

From the Centro Regional de Hemodonación, University of Murcia, Spain (LN-N, MLL, JR, JC, RG-C, VV, CM), Hematology and Medical Oncology Service, Hospital Morales Meseguer, Murcia, Spain (VR, VV), Neurology Service, Hospital Reina Sofía, Murcia, Spain (JAI), Neurovascular Research Laboratory, Neurology Service, Hospital Vall d’Hebron, Barcelona, Spain (JM).

Correspondence: Constantino Martínez, University of Murcia, Centro Regional de Hemodonación, C/Ronda de Garay S/N, Murcia-30003, Spain. E-mail: constant{at}um.es

Background and Objectives: Platelets play a fundamental role in hemostasis and alterations of their function can be determinant in the onset of stroke. A polymorphism in ß1-tubulin (TUBB1 Q43P), a protein specifically expressed in the megakaryocytic line, has been described as a protective factor in cardiovascular disease. The potential effect of this variant in the pathogenesis of hemorrhagic stroke has not yet been investigated.

Design and Methods: We evaluated the role of the TUBB1 Q43P polymorphism and its synergism with other polymorphisms in the risk of developing subarachnoid (SAH) and intracerebral hemorrhage (ICH). We performed the study in 109 patients with SAH, 259 patients with ICH, and 449 subjects from the general population from southern Spain.

Results: No relationship was found between the TUBB1 Q43P polymorphism and SAH. In contrast, this polymorphism significantly increased the risk of ICH in men (OR, 2.78; 95% CI, 1.16–6.63; p=0.021) and was associated with an earlier age of occurrence of an ICH event (p=0.011). Carriers of the TUBB1 Q43P polymorphism displayed lower platelet reactivity towards collagen. A potent synergistic effect was observed in ICH patients carrying the TUBB1 Q43P polymorphism combined with either FVII -323 Del/Ins of a decanucleotide (OR 20.76; 95% CI, 3.57–120.71; p<0.001) or FXIII V34L (OR 7.19; 95% CI, 1.99–25.95; p=0.003).

Interpretation and Conclusions: This is the first evidence linking the TUBB1 Q43P platelet polymorphism with hemorrhagic stroke in humans. The TUBB1 Q43P polymorphism, by causing a lower reactivity in platelets carrying the variant form of ß1-tubulin, protects against thrombotic disorders but increases the risk of ICH in men.

Key words: platelets, ß1-tubulin, intracerebral hemorrhage, polymorphisms, synergism.






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