Blood:FVII活性与缺血性卒中的发生密切相关

2019-02-09 MedSci MedSci原创

凝血因子VII (FVII)是凝血级联的重要组成部分。迄今为止,尚未能解析调控FVII活性和/或水平的基因位点。现Paul S. de Vries等人对9个评估血浆FVII水平的全基因组关联研究((7个关于FVII活性和2个针对FVII抗原,共包含的27495名欧洲和非洲血统的受试者)进行了Meta分析。研究人员先将欧洲人和非洲人分开进行分析,然后再一起分析。对7个评估FVII活性的研究进行主要分

凝血因子VII (FVII)是凝血级联的重要组成部分。迄今为止,尚未能解析调控FVII活性和/或水平的基因位点。现Paul S. de Vries等人对9个评估血浆FVII水平的全基因组关联研究((7个关于FVII活性和2个针对FVII抗原,共包含的27495名欧洲和非洲血统的受试者)进行了Meta分析。研究人员先将欧洲人和非洲人分开进行分析,然后再一起分析。对7个评估FVII活性的研究进行主要分析,9个研究整体分析为次要分析。

研究人员采用siRNA沉默人肝细胞系(HuH7)中的候选基因,然后检测F7 mRNA水平和FVII蛋白的表达,为新发现的重要位点提供功能性基因组验证。最后,研究人员采用Meta分析结果进行孟德尔随机化分析,来评估FVII的活性对冠状动脉疾病、缺血性卒中和静脉血栓栓塞的因果效应。

最后,研究人员鉴别出2个新的(REEP3和JAZF1-AS1)和6个已知的与FVII活性相关的位点,可解释19.0%的表型变异。将FVII抗原数据汇入Meta分析不改变上述结果。沉默HuH7的REEP3会上调FVII,而沉默JAZF1-AS1会下调FVII的表达。孟德尔随机化分析提示FVII活性与缺血性卒中正相关。REEP3和JAZF1突变可通过调节F7的表达水平影响FVII活性。FVII活性与普通人群发生缺血性卒中相关。



原始出处:

Paul S. de Vries, et al.A genome-wide association study identifies new loci for factor VII and implicates factor VII in ischemic stroke etiology. Blood 2019 :blood-2018-05-849240; doi: https://doi.org/10.1182/blood-2018-05-849240

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    2019-02-10 健健

    卒中虽然是临床上常见病,溶栓,取栓等血管内治疗也很成熟,但是仍然有很多未知问题有待认知!

    0

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    2019-02-09 天地飞扬

    了解一下,谢谢分享!

    0