The TUBB1 Q43P functional polymorphism reduces the risk of cardiovascular disease in men by modulating platelet function and structure
The TUBB1 Q43P functional polymorphism reduces the risk of cardiovascular disease in men by modulating platelet function and structure
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DOI：
10.1182/blood-2005-02-0723
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发表时间：
2005-10-01
期刊：
影响因子：
20.3
通讯作者：
Van Geet, C
中科院分区：
文献类型：
--
作者：
Freson, K;De Vos, R;Van Geet, C
血小板的盘状形式由紧密卷曲的微管边缘带维持。 β1-微管蛋白是血小板和巨核细胞微管内的主要亚型。在 33 名不相关的遗传性巨血小板减少症患者中的 24.2% 以及 272 名健康人群中的 10.6% 中，在高度保守的残基 43 中发现了 β1-微管蛋白中的 P 0 取代。Q43P 变体的杂合携带者表现出血小板蛋白 β1-微管蛋白表达减少。在巨核细胞 MEG01 细胞中转染绿色荧光蛋白 (GFP) 标记的 Q43P β 1-微管蛋白会导致微管蛋白组织紊乱。电子显微镜显示增大的球形血小板具有扰乱的边缘带和无细胞器区。此外，具有 Q43P β1-微管蛋白变体的血小板减少了三磷酸腺苷 (ATP) 分泌、凝血酶受体激活肽 (TRAP) 诱导的聚集和胶原蛋白粘附。对照受试者中 Q43P β 1-微管蛋白变异的患病率也比心血管疾病患者高 2 倍（比值比，[OR] = 2.1；95% 置信区间 [CI]，1.22-3.59）（10.4% vs 5.2%，P）
The discoid form of platelets is maintained by a marginal band of tightly coiled microtubules. beta 1-tubulln 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 healthy population a P for 0 substitution in beta 1-tubulin was found in the highly conserved residue 43. Heterozygous carriers of the Q43P variant showed a reduced platelet protein beta 1-tubulin expression. Transfection of green fluorescent protein (GFP)-tagged Q43P beta 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 beta 1-tubulin variant had reduced adenosine triphosphate (ATP) secretion, thrombin receptor activating peptide (TRAP)-induced aggregation and collagen adhesion. The prevalence of the Q43P beta 1-tubulin variant was also 2 times higher (odds ratio, [OR] = 2.1;95% confidence interval [CI], 1.22-3.59) among control subjects than among patients with cardiovascular disease (10.4% versus 5.2%, P