期刊
THROMBOSIS AND HAEMOSTASIS
卷 105, 期 5, 页码 855-863出版社
GEORG THIEME VERLAG KG
DOI: 10.1160/TH10-08-0536
关键词
Platelet ultrastructure; TUBB1 Q43P polymorphism; homozygosis
资金
- Ministerio de Ciencia e Innovacion [BES-2007-16973]
- Fundacion para la Formacion e Investigacion Sanitarias de In Region de Murcia (FFIS)
- EMBO [ASTF 385-2008]
- ISCIII [Red RECAVA RD06/0014/0039]
- FEDER [P108/1506, EMER07/035]
- Fundacion Seneca [07703/GERM/07]
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.
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