Mol Genet Genomic Med:阜外张伟丽团队首次揭示,多个易感基因、高血压和不健康生活方式让国人中风“雪上加霜”

2019-09-09 循环 中国循环杂志

一个人是否会发生脑卒中,基因-基因的交互作用在其中扮演什么角色?高血压、吸烟、饮酒、肥胖、活动得少等不良方式是否对遗传易感基因者有加性效应?

一个人是否会发生脑卒中,基因-基因的交互作用在其中扮演什么角色?高血压、吸烟、饮酒、肥胖、活动得少等不良方式是否对遗传易感基因者有加性效应?
 
近期,阜外医院张伟丽教授团队就此进行了探索并发现,脑卒中易感基因之间的交互作用与单基因相比,可导致更高的脑卒中风险;高血压和不良生活方式则会对遗传风险较高的人“雪上加霜”。
 
研究发表在Molecular Genetics & Genomic Medicine杂志。
 
这项研究中,研究者在全国多临床中心的脑卒中病例-对照研究和平均随访时间为4.5年的脑卒中队列中进行了分析,利用GMDR方法(广义多因素降维法)分析了8个基因(16个多态位点)之间的交互作用,并采用Logistic回归分析验证GMDR 的最优基因交互作用模型。
 
结果发现,VKORC1与Chr.9p21.3 间的交互作用对缺血性脑卒中风险起关键作用,VEGFA与KDR基因间的交互作用对出血性脑卒中风险起关键作用;能够显著增加遗传风险较高个体的脑卒中事件。
 
而且同时携带VKORC1 rs2359612C和Chr.9p21.3 rs10757274G基因多态位点的人,有更高的缺血性脑卒中发病风险,以及更高的脑卒中复发、脑卒中后心脑血管死亡风险,增加约2倍,并且与颈动脉内膜中层厚度(IMT)和动脉粥样硬化内膜损伤呈正相关。
 
在较高的遗传风险背景下,若存在高血压,脑卒中风险将进一步增加约10倍(OR=10.61,95%CI:6.85~16.44);若缺乏规律的体力锻炼,风险进一步增加约6倍(OR=6.15, 95% CI: 3.60~10.50)。
 
其中,VKORC1基因编码维生素K环氧化物还原酶复合体亚单位1,通过影响维生素K代谢进而影响华法林的剂量反应和凝血机制。
 
Chr.9p21.3是位于人类9号染色体短臂的基因片段,是冠心病、脑卒中的强易感基因,影响血管结构和动脉粥样硬化炎症反应。
 
VEGFA基因编码血管内皮细胞生长因子,与它的受体KDR在血管生成、损伤修复中起关键作用。
 
研究者表示,基因-基因和基因-环境之间的交互作用能够更好地预测心脑血管疾病风险,是建立多基因复杂性疾病精准诊疗预警体系的一个新领域。
 
据了解,自2002年,阜外医院张伟丽团队在科技部 973 计划(国家重点基础研究发展计划)、国家自然科学基金项目等支持下,系列研究了血管损伤与修复、凝血功能异常等重要调控基因可能作为预测缺血性或出血性脑卒中发病风险和预后的新的遗传标记。相关研究成果相继发表在Stroke, Circulation等有影响力的国际期刊上。

原始出处:
Feng C, Yang Y, Yang S,Tu X, Wang Y, Song Y, Hui R, Zhang W. Effect of gene-gene and gene-environment interaction on the risk of first-ever stroke and poststroke death. Mol Genet Genomic Med, 2019, 7(8): e846.

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    2020-05-12 cy0324
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  4. [GetPortalCommentsPageByObjectIdResponse(id=2049222, encodeId=249220492220f, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7929, encryptionId=4363e929ad, topicName=Gene)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=63a4277, createdName=cy0324, createdTime=Tue May 12 10:04:00 CST 2020, time=2020-05-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1660914, encodeId=fa4b1660914a6, content=<a href='/topic/show?id=a38b2e8752d' target=_blank style='color:#2F92EE;'>#健康生活#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27875, encryptionId=a38b2e8752d, topicName=健康生活)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=48dd25178476, 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encryptionId=d4f412668a4, topicName=NET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7ea033781210, createdName=canlab, createdTime=Thu Apr 09 14:04:00 CST 2020, time=2020-04-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1371973, encodeId=37f413e19733c, content=<a href='/topic/show?id=ec702e877fb' target=_blank style='color:#2F92EE;'>#健康生活方式#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27877, encryptionId=ec702e877fb, topicName=健康生活方式)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f612331, createdName=gds2009, createdTime=Wed Sep 11 13:04:00 CST 2019, time=2019-09-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1394458, encodeId=2eb5139445867, content=<a href='/topic/show?id=7deb59659b9' target=_blank style='color:#2F92EE;'>#易感基因#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=59659, encryptionId=7deb59659b9, topicName=易感基因)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/101296147/72D57F5B3E12B2BB53D6BD015D14DCD6/100, createdBy=a92e2500162, createdName=passed water, createdTime=Wed Sep 11 13:04:00 CST 2019, time=2019-09-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1609978, encodeId=15de16099e8a4, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=552a19396740, createdName=ms3994565386320060, createdTime=Wed Sep 11 13:04:00 CST 2019, time=2019-09-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1045895, encodeId=3c2810458955c, 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=44, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=guging, createdTime=Tue Sep 10 01:04:00 CST 2019, time=2019-09-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=372517, encodeId=ebd83e2517a1, content=学习了,很有用,不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib3IzoRn621JdKCFUI4XvNELcibocrAVU6aUzEVDSaf3rYH08PUYUiagGqxAEhj8g9WqqNvD1CupIpCrmnR2OrqHZh/0, createdBy=7f181365728, createdName=飛歌, createdTime=Tue Sep 10 00:16:15 CST 2019, time=2019-09-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=372515, encodeId=80a13e25151b, content=好, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/07/01/577acf4668c2eb760152040cdd4c4196.jpg, createdBy=dc3f5107879, createdName=最帅小男护, createdTime=Tue Sep 10 00:02:16 CST 2019, time=2019-09-10, status=1, ipAttribution=)]
    2020-04-09 canlab
  5. [GetPortalCommentsPageByObjectIdResponse(id=2049222, encodeId=249220492220f, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7929, encryptionId=4363e929ad, topicName=Gene)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=63a4277, createdName=cy0324, createdTime=Tue May 12 10:04:00 CST 2020, time=2020-05-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1660914, encodeId=fa4b1660914a6, content=<a href='/topic/show?id=a38b2e8752d' target=_blank style='color:#2F92EE;'>#健康生活#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27875, encryptionId=a38b2e8752d, topicName=健康生活)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=48dd25178476, 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GetPortalCommentsPageByObjectIdResponse(id=372515, encodeId=80a13e25151b, content=好, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/07/01/577acf4668c2eb760152040cdd4c4196.jpg, createdBy=dc3f5107879, createdName=最帅小男护, createdTime=Tue Sep 10 00:02:16 CST 2019, time=2019-09-10, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=2049222, encodeId=249220492220f, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7929, encryptionId=4363e929ad, topicName=Gene)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=63a4277, createdName=cy0324, createdTime=Tue May 12 10:04:00 CST 2020, time=2020-05-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1660914, encodeId=fa4b1660914a6, content=<a href='/topic/show?id=a38b2e8752d' target=_blank style='color:#2F92EE;'>#健康生活#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27875, encryptionId=a38b2e8752d, topicName=健康生活)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=48dd25178476, 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encryptionId=d4f412668a4, topicName=NET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7ea033781210, createdName=canlab, createdTime=Thu Apr 09 14:04:00 CST 2020, time=2020-04-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1371973, encodeId=37f413e19733c, content=<a href='/topic/show?id=ec702e877fb' target=_blank style='color:#2F92EE;'>#健康生活方式#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27877, encryptionId=ec702e877fb, topicName=健康生活方式)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f612331, createdName=gds2009, createdTime=Wed Sep 11 13:04:00 CST 2019, time=2019-09-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1394458, encodeId=2eb5139445867, content=<a href='/topic/show?id=7deb59659b9' target=_blank style='color:#2F92EE;'>#易感基因#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=59659, encryptionId=7deb59659b9, topicName=易感基因)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/101296147/72D57F5B3E12B2BB53D6BD015D14DCD6/100, createdBy=a92e2500162, createdName=passed water, createdTime=Wed Sep 11 13:04:00 CST 2019, time=2019-09-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1609978, encodeId=15de16099e8a4, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=552a19396740, createdName=ms3994565386320060, createdTime=Wed Sep 11 13:04:00 CST 2019, time=2019-09-11, status=1, ipAttribution=), 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  7. [GetPortalCommentsPageByObjectIdResponse(id=2049222, encodeId=249220492220f, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7929, encryptionId=4363e929ad, topicName=Gene)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=63a4277, createdName=cy0324, createdTime=Tue May 12 10:04:00 CST 2020, time=2020-05-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1660914, encodeId=fa4b1660914a6, content=<a href='/topic/show?id=a38b2e8752d' target=_blank style='color:#2F92EE;'>#健康生活#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27875, encryptionId=a38b2e8752d, topicName=健康生活)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=48dd25178476, 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encryptionId=d4f412668a4, topicName=NET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7ea033781210, createdName=canlab, createdTime=Thu Apr 09 14:04:00 CST 2020, time=2020-04-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1371973, encodeId=37f413e19733c, content=<a href='/topic/show?id=ec702e877fb' target=_blank style='color:#2F92EE;'>#健康生活方式#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27877, encryptionId=ec702e877fb, topicName=健康生活方式)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f612331, createdName=gds2009, createdTime=Wed Sep 11 13:04:00 CST 2019, time=2019-09-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1394458, encodeId=2eb5139445867, content=<a href='/topic/show?id=7deb59659b9' target=_blank style='color:#2F92EE;'>#易感基因#</a>, beContent=null, objectType=article, 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GetPortalCommentsPageByObjectIdResponse(id=372515, encodeId=80a13e25151b, content=好, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/07/01/577acf4668c2eb760152040cdd4c4196.jpg, createdBy=dc3f5107879, createdName=最帅小男护, createdTime=Tue Sep 10 00:02:16 CST 2019, time=2019-09-10, status=1, ipAttribution=)]
  8. [GetPortalCommentsPageByObjectIdResponse(id=2049222, encodeId=249220492220f, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7929, encryptionId=4363e929ad, topicName=Gene)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=63a4277, createdName=cy0324, createdTime=Tue May 12 10:04:00 CST 2020, time=2020-05-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1660914, encodeId=fa4b1660914a6, content=<a href='/topic/show?id=a38b2e8752d' target=_blank style='color:#2F92EE;'>#健康生活#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27875, encryptionId=a38b2e8752d, topicName=健康生活)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=48dd25178476, 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GetPortalCommentsPageByObjectIdResponse(id=372515, encodeId=80a13e25151b, content=好, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/07/01/577acf4668c2eb760152040cdd4c4196.jpg, createdBy=dc3f5107879, createdName=最帅小男护, createdTime=Tue Sep 10 00:02:16 CST 2019, time=2019-09-10, status=1, ipAttribution=)]
    2019-09-10 guging

    中风是俗称,应该称为缺血性卒中吧

    0

  9. 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    2019-09-10 飛歌

    学习了,很有用,不错

    0

  10. 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GetPortalCommentsPageByObjectIdResponse(id=372515, encodeId=80a13e25151b, content=好, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/07/01/577acf4668c2eb760152040cdd4c4196.jpg, createdBy=dc3f5107879, createdName=最帅小男护, createdTime=Tue Sep 10 00:02:16 CST 2019, time=2019-09-10, status=1, ipAttribution=)]
    2019-09-10 最帅小男护

    0

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每年有3800万人死于可预防的非传染性疾病,其中大多数是心血管疾病。有几个有充分记录的干预措施有望预防大量这类死亡,但有很大一部分需要帮助的人群无法获得这些干预措施。研究人员对3种高影响和可行的干预措施对全球死亡率的影响进行量化评估:将高血压治疗比例提高到70%、减少30%的钠摄入量、不摄入人工反式脂肪酸。研究人员采用全球数据,预测从2015年到2040年全球各国的特定原因的死亡率。三种干预措施的

Lancet:基于社区的高血压心血管风险综合干预

研究认为,非内科医生保健工作者(NPHW)、初级保健医生、家庭和提供有效药物的模式可大大改善了血压控制和心血管疾病风险

高血压中医诊疗专家共识

高血压已成为全球重大公共卫生问题。为提高中医药防治高血压的临床与科研水平,规范中医药在高血压中的运用,受中华中医药学会心血管病分会委托,以传统中医辨证论治与方证辨证理论为指导,结合现代循证医学理念,通过对历代文献的系统梳理,尤其是近30 年来高血压文献的回顾分析,深入挖掘名老中医经验,先后开展数次专家咨询,对高血压的关键病机、证候特点、经典名方辨证用药规律进行归纳、总结,讨论并制定高血压中医诊疗专

Eur Heart J:牙周炎与高血压之间的因果关系

由此可见,该研究观察到牙周炎和BP之间的因果关系。