Stroke:血浆微小RNA可预测脑卒中风险

2021-02-16 Freeman MedSci原创

血浆微小RNA可预测脑卒中风险

虽然环境和血管风险因素参与了脑卒中的病理过程,但遗传因素也是缺血性和出血性脑卒中发病风险的原因之一。已有研究表明,不仅编码基因,特别是12q24.2和ABO等位点,占可遗传风险的一部分,而且基因组的非编码区域,如microRNAs(miRNAs),也可以在卒中的病理生理学中发挥作用。更好地了解miRNAs在卒中发展中的作用及其作为生物标志物在疾病诊断中的潜力,可以早期发现具有高危特征的个体。

miRNAs是≈22个核苷酸的小型非编码RNA分子,通过与目标转录本的互补结合来调节转录后的基因表达。它们可以潜在地靶向数百到数千个基因,并参与各种分子途径。除了在疾病和非疾病状态下能够调节细胞过程外,miRNAs还从细胞中释放到体液中,如血浆中。 这些循环miRNAs在血浆中非常稳定,由于它们被包装成包括外植体在内的膜性小体,因此作为疾病的生物标志物具有潜在的临床意义。

以前的研究已经将血浆miRNA水平的变化与心血管疾病和中风联系起来。大多数与卒中相关的miRNAs都是在急性卒中患者队列中交叉鉴定的,这使得所鉴定的miRNAs是否与发生卒中的风险相关尚不确定。

而前瞻性队列可以克服这一局限性。事实上,最近一项样本量不大的纵向研究(n=51例)发现,平均随访时间为2.5±1.6年,miR-656-3p和miR-941的血浆水平与卒中事件之间存在关联。然而,随访时间相对较长的纵向研究有限。

藉此,荷兰鹿特丹大学的Michelle M.J. Mens等人,在基于人群的前瞻性研究中(Rotterdam study)确定了循环miRNAs与所有卒中及其亚型风险之间的关联,随访时间近10年。随后,他们对miRNA推测的靶基因进行了后续分析,以深入了解所确定的miRNAs可能在卒中中发挥作用的潜在途径。


通过利用下一代测序测量2002年至2005年收集的血浆样本中2083个miRNAs的表达水平,这些样本来自鹿特丹研究的1914名无卒中参与者。

通过对医疗记录的连续监测,对参与者进行评估是否发生卒中,时间截止到2016年1月1日。采用经年龄、性别和血管风险因素调整的Cox比例危险回归模型,调查血浆中表达良好的591个miRNAs水平与事件性卒中之间的关系。此外,还进行了卒中亚型分析,以评估已确定的miRNAs与缺血性、出血性和未明确的卒中之间的联系。随后,进行了后续分析,以深入了解miRNAs的假定靶基因与卒中之间的关联。

结果显示:
在1914名参与者(平均年龄71.5岁±7.6岁;57.7%为女性)中,138人在平均随访9.7±3.2年期间被诊断为新发卒中。调整潜在混杂因素后,发现3种miRNA的血浆水平与事件性卒中相关。这些包括miR-6124(HR=1.66、miR-5196-5p(HR1.9)和miR-4292(HR=2.65)。

对这些miRNAs的假定靶基因进行的硅片分析(in silico)显示,发现了几个靶基因的变异与卒中有关。

这个研究的重要意义在于:发现了血浆中3种特异的miRNAs的水平与卒中风险相关,提出它们是早期检测疾病的潜在生物标志物。

原文出处:

Mens, M. M., Heshmatollah, A., Fani, L., Ikram, M. A., Ikram, M. K., & Ghanbari, M. (2021). Circulatory MicroRNAs as Potential Biomarkers for Stroke Risk: The Rotterdam Study. _Stroke_, STROKEAHA-120.

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    2021-02-17 bshuang
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    2021-02-17 花花1372
  4. [GetPortalCommentsPageByObjectIdResponse(id=1281359, encodeId=460c128135943, content=<a href='/topic/show?id=455f36085f0' target=_blank style='color:#2F92EE;'>#卒中风险#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=36085, encryptionId=455f36085f0, topicName=卒中风险)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Wed Feb 17 22:03:20 CST 2021, time=2021-02-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1399495, encodeId=98ed1399495bc, content=<a href='/topic/show?id=c7fc5058804' target=_blank style='color:#2F92EE;'>#微小RNA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=50588, encryptionId=c7fc5058804, topicName=微小RNA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=21e42213106, createdName=bshuang, createdTime=Wed Feb 17 22:03:20 CST 2021, time=2021-02-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1604226, encodeId=d433160422629, content=<a href='/topic/show?id=a2df4684e9a' target=_blank style='color:#2F92EE;'>#小RNA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=46847, encryptionId=a2df4684e9a, topicName=小RNA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2c9119152195, createdName=花花1372, createdTime=Wed Feb 17 22:03:20 CST 2021, time=2021-02-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1026768, encodeId=69671026e6807, content=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!, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=健健, createdTime=Tue Feb 16 10:03:20 CST 2021, time=2021-02-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1046021, encodeId=012e104602110, content=中风是俗称,应该称为缺血性卒中吧, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=guging, createdTime=Tue Feb 16 10:03:20 CST 2021, time=2021-02-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=924842, encodeId=735292484244, content=学习了<a href='/topic/show?id=23e3454e353' target=_blank style='color:#2F92EE;'>#学习#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=45473, encryptionId=23e3454e353, topicName=学习)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2c975456358, createdName=ms1000000686260508, createdTime=Tue Feb 16 08:29:31 CST 2021, time=2021-02-16, status=1, ipAttribution=)]
    2021-02-16 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

  5. [GetPortalCommentsPageByObjectIdResponse(id=1281359, encodeId=460c128135943, content=<a href='/topic/show?id=455f36085f0' target=_blank style='color:#2F92EE;'>#卒中风险#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=36085, encryptionId=455f36085f0, topicName=卒中风险)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Wed Feb 17 22:03:20 CST 2021, time=2021-02-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1399495, encodeId=98ed1399495bc, content=<a href='/topic/show?id=c7fc5058804' target=_blank style='color:#2F92EE;'>#微小RNA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=50588, encryptionId=c7fc5058804, topicName=微小RNA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=21e42213106, createdName=bshuang, createdTime=Wed Feb 17 22:03:20 CST 2021, time=2021-02-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1604226, encodeId=d433160422629, content=<a href='/topic/show?id=a2df4684e9a' target=_blank style='color:#2F92EE;'>#小RNA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=46847, encryptionId=a2df4684e9a, topicName=小RNA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2c9119152195, createdName=花花1372, createdTime=Wed Feb 17 22:03:20 CST 2021, time=2021-02-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1026768, encodeId=69671026e6807, content=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!, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=健健, createdTime=Tue Feb 16 10:03:20 CST 2021, time=2021-02-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1046021, encodeId=012e104602110, content=中风是俗称,应该称为缺血性卒中吧, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=guging, createdTime=Tue Feb 16 10:03:20 CST 2021, time=2021-02-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=924842, encodeId=735292484244, content=学习了<a href='/topic/show?id=23e3454e353' target=_blank style='color:#2F92EE;'>#学习#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=45473, encryptionId=23e3454e353, topicName=学习)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2c975456358, createdName=ms1000000686260508, createdTime=Tue Feb 16 08:29:31 CST 2021, time=2021-02-16, status=1, ipAttribution=)]
    2021-02-16 guging

    中风是俗称,应该称为缺血性卒中吧

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1281359, encodeId=460c128135943, content=<a href='/topic/show?id=455f36085f0' target=_blank style='color:#2F92EE;'>#卒中风险#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=36085, encryptionId=455f36085f0, topicName=卒中风险)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Wed Feb 17 22:03:20 CST 2021, time=2021-02-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1399495, encodeId=98ed1399495bc, content=<a href='/topic/show?id=c7fc5058804' target=_blank style='color:#2F92EE;'>#微小RNA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=50588, encryptionId=c7fc5058804, topicName=微小RNA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=21e42213106, createdName=bshuang, createdTime=Wed Feb 17 22:03:20 CST 2021, time=2021-02-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1604226, encodeId=d433160422629, content=<a href='/topic/show?id=a2df4684e9a' target=_blank style='color:#2F92EE;'>#小RNA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=46847, encryptionId=a2df4684e9a, topicName=小RNA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2c9119152195, createdName=花花1372, createdTime=Wed Feb 17 22:03:20 CST 2021, time=2021-02-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1026768, encodeId=69671026e6807, content=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!, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=健健, createdTime=Tue Feb 16 10:03:20 CST 2021, time=2021-02-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1046021, encodeId=012e104602110, content=中风是俗称,应该称为缺血性卒中吧, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=guging, createdTime=Tue Feb 16 10:03:20 CST 2021, time=2021-02-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=924842, encodeId=735292484244, content=学习了<a href='/topic/show?id=23e3454e353' target=_blank style='color:#2F92EE;'>#学习#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=45473, encryptionId=23e3454e353, topicName=学习)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2c975456358, createdName=ms1000000686260508, createdTime=Tue Feb 16 08:29:31 CST 2021, time=2021-02-16, status=1, ipAttribution=)]
    2021-02-16 ms1000000686260508

    学习了#学习#

    0

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