Clinical Translational Gastroenterology: DNA甲基化特征的鉴定及其在克罗恩病中的临床价值

2019-12-11 不详 MedSci原创

DNA甲基化是调节基因表达的表观遗传机制,代表了基因型,环境和疾病之间的重要联系。这是一种可逆和可遗传的机制,也许可以为治疗某种疾病提供目标。本项研究旨在评估以前与克罗恩病(CD)相关的特定基因的甲基化变化,并研究它们与病理的可能关联。

背景及目的:
DNA甲基化是调节基因表达的表观遗传机制,代表了基因型,环境和疾病之间的重要联系。这是一种可逆和可遗传的机制,也许可以为治疗某种疾病提供目标。本项研究旨在评估以前与克罗恩病(CD)相关的特定基因的甲基化变化,并研究它们与病理的可能关联。

方法:
本项研究纳入了103名参与者,将他们分为2个队列(第一个模型队列[n = 31]和第二个验证队列[n = 72]),其中包括了活跃CD(aCD)和非活跃CD(iCD)以及健康参与者(CTR) 。从所有受试者中的外周血中获得DNA,并通过Agena平台进行分析。选择的基因为过氧化氢酶(CAT),α-防御素5(DEFA5),FasR,FasL,肿瘤坏死因子(TNF),TNFRSF1A,TNFRSF1B,PPA2,ABCB1,NOD2,PPARγ。

结果:
研究发现16种CpG在aCD,iCD和CTR中显示出不同的甲基化特征。研究人员选择了差异最大的那些进行验证:DEFA5 CpG_11; CpG_13; CAT CpG_31.32; TNF CpG_4,CpG_12;和ABCB1 CpG_21。结果验证为DEFA5(甲基化增加)和TNF(甲基化损失)的基因,P值<0.001。在这两种情况下,甲基化水平均保持不变,且不会随CD活性而变化(aCD与iCD)。

讨论:
DEFA5和TNF基因的甲基化状态提供了标志性生物标志物,可鉴别CD患者并支持CD发病机制中环境和免疫系统的可能作用。

原始出处:
Moret-Tatay. Et al. Identification of Epigenetic Methylation Signatures With Clinical Value in Crohn's Disease. Clinical Translational Gastroenterology.2019.

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    2020-01-22 许安
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createdBy=d81c2500028, createdName=12498561m32(暂无昵称), createdTime=Fri Mar 20 13:12:00 CST 2020, time=2020-03-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2067482, encodeId=67ea206e482de, content=<a href='/topic/show?id=d0841e75535' target=_blank style='color:#2F92EE;'>#Transl#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17755, encryptionId=d0841e75535, topicName=Transl)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdqq.qlogo.cn/qqapp/101173734/363C99735735B7F4CB11D5F78F580525/100, createdBy=aab22500211, createdName=ms3025846204744509, createdTime=Mon Apr 27 14:12:00 CST 2020, time=2020-04-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1657272, encodeId=a500165e27261, content=<a href='/topic/show?id=3ca31e71903' target=_blank style='color:#2F92EE;'>#TRA#</a>, beContent=null, objectType=article, 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content=<a href='/topic/show?id=440a226e6c4' target=_blank style='color:#2F92EE;'>#临床价值#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=22676, encryptionId=440a226e6c4, topicName=临床价值)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/vLodSSFTQLpHtfwJicWJibSWH7pbiauxvpCMvQIv0N9Oes8vHkDkCIW2HNDkt7icUq3RCZiaDcHR9Rap17fFySRbiaFg/132, createdBy=9f202500205, createdName=ms3297076796458174, createdTime=Thu Nov 05 00:12:00 CST 2020, time=2020-11-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1795892, encodeId=56061e9589212, content=<a href='/topic/show?id=42211e757d7' target=_blank style='color:#2F92EE;'>#Translation#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17757, encryptionId=42211e757d7, 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content=<a href='/topic/show?id=7730e85412' target=_blank style='color:#2F92EE;'>#Gastroenterology#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7854, encryptionId=7730e85412, topicName=Gastroenterology)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=5fc29706655, createdName=chaojitidian, createdTime=Fri Dec 13 03:12:00 CST 2019, time=2019-12-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1507688, encodeId=993e150e688cb, content=<a href='/topic/show?id=8764484014' target=_blank style='color:#2F92EE;'>#clinical#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4840, encryptionId=8764484014, topicName=clinical)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=1ee59933733, createdName=zll0628, createdTime=Fri Dec 13 03:12:00 CST 2019, time=2019-12-13, status=1, ipAttribution=)]
    2020-11-17 bsmagic9140
  5. 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createdBy=d81c2500028, createdName=12498561m32(暂无昵称), createdTime=Fri Mar 20 13:12:00 CST 2020, time=2020-03-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2067482, encodeId=67ea206e482de, content=<a href='/topic/show?id=d0841e75535' target=_blank style='color:#2F92EE;'>#Transl#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17755, encryptionId=d0841e75535, topicName=Transl)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdqq.qlogo.cn/qqapp/101173734/363C99735735B7F4CB11D5F78F580525/100, createdBy=aab22500211, createdName=ms3025846204744509, createdTime=Mon Apr 27 14:12:00 CST 2020, time=2020-04-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1657272, encodeId=a500165e27261, content=<a href='/topic/show?id=3ca31e71903' target=_blank style='color:#2F92EE;'>#TRA#</a>, beContent=null, objectType=article, 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content=<a href='/topic/show?id=7730e85412' target=_blank style='color:#2F92EE;'>#Gastroenterology#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7854, encryptionId=7730e85412, topicName=Gastroenterology)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=5fc29706655, createdName=chaojitidian, createdTime=Fri Dec 13 03:12:00 CST 2019, time=2019-12-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1507688, encodeId=993e150e688cb, content=<a href='/topic/show?id=8764484014' target=_blank style='color:#2F92EE;'>#clinical#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4840, encryptionId=8764484014, topicName=clinical)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=1ee59933733, createdName=zll0628, createdTime=Fri Dec 13 03:12:00 CST 2019, time=2019-12-13, status=1, ipAttribution=)]
  6. 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  7. 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