Browsing by Author "Vicente, Vicente"

Now showing 1 - 4 of 4
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    Genotype-phenotype relationship for six common polymorphisms in genes affecting platelet function from 286 healthy subjects and 160 patients with mucocutaneous bleeding of unknown cause
    (2009) Martínez, Constantino; Antón, Ana Isabel; Corral, Javier; Quiroga Gutiérrez, Sara Teresita; Panes Becerra, Olga Teresa; Lozano, María Luisa; González Conejero, Rocío; Teruel, Raúl; Navarro Núñez, Leyre; Pereira Garcés, Jaime Ignacio; Mezzano, Diego; Vicente, Vicente; Rivera, José
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    Influence of the F12-4 C > T polymorphism on hemostatic tests
    (LIPPINCOTT WILLIAMS & WILKINS, 2010) Corral, Javier; Anton, Ana I.; Quiroga, Teresa; Gonzalez Conejero, Rocio; Pereira, Jaime; Roldan, Vanessa; Vicente, Vicente; Mezzano, Diego
    The common F12 - 4 C>T polymorphism significantly regulates plasma levels of FXII, the first element of the intrinsic pathway of coagulation. Due to the robust effects that this pathway has on blood coagulation in vitro, the objective of our study was to evaluate the influence of this polymorphism on different hemostatic tests. We studied 46 hemostatic parameters in 566 participants: 280 patients with mucocutaneous bleeding and 286 controls. The F12 - 4T allele, associated with reduced levels of FXII (P<0.001), also significantly delayed the activated partial thromboplastin time (aPTT) expressed as aPTTr (ratio sample plasma/normal pooled plasma). Thus, both patients and controls carrying the T allele had higher aPTTr than C/C homozygous individuals (P<0.001). Interestingly, 92% of healthy controls who had prolonged aPTTr carried the F12 - 4T allele. Moreover, individuals with the F12 - 4T allele also had less thrombin generation (assessed by endogenous thrombin potential, thrombin peak and time to achieve the peak of thrombin) using a test with low tissue factor concentration and explicit contact phase activation. Finally, both patients and controls carrying the F12 - 4T allele also displayed significantly lower FIXc and FVIIc levels than C/C individuals (P<0.01). For all associations except for FVIIc, a gene-dosage effect was observed, and homozygous TT individuals had the farthest values. Our study reveals a significant effect of the F12 - 4 C>T polymorphism on hemostatic tests widely used in routine clinical practice. Blood Coagul Fibrinolysis 21: 632-639 (c) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.
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    Novel loci involved in platelet function and platelet count identified by a genome-wide study performed in children
    (FERRATA STORTI FOUNDATION, 2011) Guerrero, Jose A.; Rivera, Jose; Quiroga, Teresa; Martinez Perez, Angel; Isabel Anton, Ana; Martinez, Constantino; Panes, Olga; Vicente, Vicente; Mezzano, Diego; Soria, Jose Manuel; Corral, Javier
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    Rare homozygous status of P43 beta 1-tubulin polymorphism causes alterations in platelet ultrastructure
    (GEORG THIEME VERLAG KG, 2011) Navarro Nunez, Leyre; Teruel, Raul; Isabel Anton, Ana; Nurden, Paquita; Martinez Martinez, Irene; Luisa Lozano, Maria; Rivera, Jose; Corral, Javier; Mezzano, Diego; Vicente, Vicente; Martinez, Constantino
    beta 1-tubulin is the main constituent of the platelet marginal band and studies with deficient mice showed that it maintains discoid shape and it is required for normal platelet formation. TUBB1 Q43P polymorphism is associated with decreased beta 1-tubulin expression, diminished platelet reactivity, and partial loss of discoid shape in heterozygous carriers. However, to date no studies have been carried out on homozygous PP individuals. Our study included 19 subjects genotyped for TUBB1 Q43P polymorphism (4 QQ, 4 QP, and 2 PP). The two PP individuals were recruited after genotyping of 2073 individuals. Biochemical, microscopy, and molecular studies were performed. Real-time PCR showed a similar to 40% decrease in TUBB1 mRNA in the two PP individuals compared to four QQ subjects. Western blot analysis confirmed this reduction. Electron microscopy revealed a majority of normal discoid platelets in PP individuals, although platelets with loose, re-orientated or invaginated protofilaments, and an over-developed open canalicular system were observed. Such abnormalities were not observed in QQ subjects. Morphometric analyses showed no differences between PP and QQ individuals. Immunofluorescence confirmed the presence of a normal marginal band in a majority of platelets from PP subjects. Interestingly, both PP subjects had a 40% lower platelet count than QP and QQ. TUBB1 Q43P polymorphism in homozygosity mildly affects platelet ultrastructure and our data further suggest that high levels of beta 1-tubulin might not be critical to sustain platelet discoid shape.