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影响MPV和PLT数量的基因组变异与缺血性中风及其亚型的发展有关

Abhilash Ludhiadch¹, Sulena², Sandeep Singh³

¹Complex Disease Genomics and Precision Medicine Laboratory, Department of Human Genetics and Molecular Medicine, Central University of Punjab, Ghudda, Bathinda, Punjab, 151401, India.

Molecular neurobiology

|July 15, 2023

概括

遗传变异影响血小板计数和血小板平均体积 (MPV),影响缺血性中风风险. 高MPV受这些遗传因素的影响,可以作为缺血性中风的生物标志物,并指导治疗策略.

科学领域:

心血管研究研究心血管研究
遗传学和基因组学遗传学和基因组学
血液学血液学血液学

背景情况:

血小板在缺血性中风 (IS) 病理生理学中至关重要,特别是在动脉样硬化斑块的血栓形成中.
血小板数 (PLT) 和平均血小板体积 (MPV) 是血小板功能的关键决定因素.
了解基因对这些参数的影响对于IS研究至关重要.

研究的目的:

调查遗传变异与缺血性中风中的MPV/PLT数量之间的关联.
探索已识别的基因变异对血小板参数和蛋白质相互作用的功能影响.
评估MPV和基因标记物作为IS生物标记物的潜力.

主要方法:

使用流细胞计量和细胞计数器测量MPV和PLT计数.
索诺克洛特分析评估了凝块时间和血小板功能.
使用了基因型鉴定 (GSA,桑格测序),RT-PCR和in silico分析 (GROMACS,UNAFold,STRING) 的方法.

主要成果:

在THPO (rs6141) 和ARHGEF3 (rs1354034) 多态和IS及其亚型之间发现了显著的关联.
改变的基因型与增加的MPV,减少的PLT数量和减少的凝血率 (CR) 相关联.
在分析表明,THPO突变影响蛋白质结构,ARHGEF3突变增加mRNA半衰期,影响血小板功能.

结论:

遗传变异,特别是THPO和ARHGEF3,通过影响MPV,在缺血性中风的发展中发挥作用.
受遗传因素影响的更高的MPV可以作为缺血性中风的潜在生物标志物.
针对改变的基因型和升高的MPV可能为缺血性中风提供新的治疗途径.

关键词:

基因型基因型基因型缺血性中风是因为缺血性中风.这是一个MPV,MPV.血小板是血小板的组成部分.

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