![]() ![]() 4 This polymorphism affects a highly conserved residue within a region implicated in the binding of β1-tubulin with other isoforms of tubulin. 6 Interestingly, platelets carrying the TUBB1 Q43P polymorphism have a phenotype similar to that of the platelets from β1-tubulin-deficient mice. It has been shown that β1-tubulin-deficient mice develop thrombocytopenia with spherical platelets that are less responsive to thrombin activation. However, little is known about the role of β1-tubulin in platelet activation and aggregation. ![]() 7 In platelets, microtubules form a subcortical ring, called the marginal band, which maintains the discoid form of platelets. 5, 6 Microtubules play an important role in megakaryocyte physiology, being an essential element during thrombocytopoiesis, involved in proplatelet elongation, granule trafficking, and platelet separation. 4 This isoform of tubulin is specifically expressed in platelets and megakaryocytes and, together with α-tubulin, forms heterodimers which assemble into high-ordered microtubule polymers. ![]() Recently, a polymorphism affecting platelet function, TUBB1 Q43P, was characterized in β1-tubulin. 3 In the last years, studies have investigated the role that genetic alterations which increase platelet reactivity play in the risk of thrombosis, while the role of genetic changes leading to platelet hyporeactivity in the development of hemorrhagic disorders has been rarely surveyed. 1– 3 In particular, patients with atherosclerotic plaque rupture show an enhanced platelet activation and have increased amounts of platelet-leukocyte aggregates. In addition, platelets with a more reactive state play an important role in stroke events. Platelets play a critical role in hemostasis through the formation of the hemostatic plug at sites of vessel injury. The TUBB1 Q43P polymorphism, by causing a lower reactivity in platelets carrying the variant form of β1-tubulin, protects against thrombotic disorders but increases the risk of ICH in men. Interpretation and Conclusions This is the first evidence linking the TUBB1 Q43P platelet polymorphism with hemorrhagic stroke in humans. 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). ![]() Carriers of the TUBB1 Q43P polymorphism displayed lower platelet reactivity towards collagen. 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). Results No relationship was found between the TUBB1 Q43P polymorphism and SAH. We performed the study in 109 patients with SAH, 259 patients with ICH, and 449 subjects from the general population from southern Spain. 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). The potential effect of this variant in the pathogenesis of hemorrhagic stroke has not yet been investigated. A polymorphism in β1-tubulin (TUBB1 Q43P), a protein specifically expressed in the megakaryocytic line, has been described as a protective factor in cardiovascular disease. Abstract Background and Objectives Platelets play a fundamental role in hemostasis and alterations of their function can be determinant in the onset of stroke. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |