movement disorders:吸烟和基因相互作用,或促进帕金森发生

2022-07-26 Freeman MedSci原创

尽管这是PD研究中最有力的发现之一,但吸烟和PD之间的逆向关联的机制仍然未知

帕金森病(PD)的全基因组关联研究(GWAS)确定了与人类白细胞抗原(HLA)区域,特别是与HLADRB1的关联。Hollenbach等人报告了PD与共享表位(SE)的逆向关联,共享表位是HLA-DRB1编码的氨基酸(AA)组合,只有在11位有缬氨酸的情况下(V11)。在一项跨种族的GWAS荟萃分析中,最强的关联是与HLA-DRB1中第13位的组氨酸(H13)的逆向关联,与V11密切相关。最新的研究与前两项研究有一些重叠,强调了HLA-DRB1编码的三个AA(V11、H13和H33)与PD呈反比关系。

 

图1: 论文封面图

继研究显示吸烟和HLA-DRB1在其他情况下的相互作用后,Chuang等人对HLA-DRB1区域的一个单核苷酸多态性(SNP)进行了基因分型,其小G等位基因与PD呈反比关系(2056例,2723例对照),并报告了自我报告的吸烟和rs660895-G之间的显著正向相互作用:与G等位基因携带者相比,吸烟和PD的反比关系更为强烈。

基于一个较小的选定样本(837例,918例对照),发现SE和V11组合(SE+V11+)与PD的逆向关联的研究也显示了与吸烟的相互作用,但方向相反:吸烟与PD的逆向关联仅限于SE+V11+携带者。作者推测,吸烟诱导的α-突触核蛋白的翻译后修饰(瓜氨酸化/高瓜氨酸化)解释了这种互动。

法国 Univ. Paris-Sud的Cloé Domenighetti等人,对HLA-DRB1吸烟的相互作用进行了大规模的独立复制,在HLA-DRB1定义的阶层中使用吸烟易感基因作为工具变量进行了孟德尔随机化(MR)分析。

他们对12 424个病例和9480个对照组中与吸烟开始有关的182个单核苷酸多态性(SNPs)进行基因分型,在由HLA-DRB1定义的阶层中进行孟德尔随机化(MR)分析。

在氨基酸水平上,HLA-DRB1中第11位的缬氨酸(V11)与PD显示出最强的关联。MR显示,只有在没有V11的情况下,基因预测的吸烟开始与PD之间才有逆向关联(HR=0.74,95%置信区间,0.59-0.93,PInteraction = 0.028)。

图2:论文结果图

对V11和吸烟引起的α-突触核苷酸修饰对结合亲和力的影响进行硅学预测,结果与这种相互作用模式一致。

该研究的重要意义在于发现了:尽管这是PD研究中最有力的发现之一,但吸烟和PD之间的逆向关联的机制仍然未知。该发现可能有助于更好地理解这种关联。


原文出处:
Domenighetti C, Douillard V, Sugier P, et al. The Interaction between _HLA‐DRB1_ and Smoking in Parkinson’s Disease Revisited. _Movement Disorders_. Published online July 10, 2022:mds.29133. doi:[10.1002/mds.29133](https://doi.org/10.1002/mds.29133)

 

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    2023-04-07 anminleiryan
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  5. [GetPortalCommentsPageByObjectIdResponse(id=1738147, encodeId=8da71e381473e, content=<a href='/topic/show?id=e10b600329' target=_blank style='color:#2F92EE;'>#disorders#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6003, encryptionId=e10b600329, topicName=disorders)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=efbf34357637, createdName=ms2186806800017884, createdTime=Tue Dec 27 03:23:05 CST 2022, time=2022-12-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1909341, encodeId=ae9a190934142, content=<a href='/topic/show?id=8039e2512e8' target=_blank style='color:#2F92EE;'>#相互作用#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72512, encryptionId=8039e2512e8, topicName=相互作用)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=hb2008ye, createdTime=Mon Dec 05 18:23:05 CST 2022, time=2022-12-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1878565, encodeId=105e18e8565a1, content=<a href='/topic/show?id=c157696175' target=_blank style='color:#2F92EE;'>#ERS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6961, encryptionId=c157696175, topicName=ERS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e93e105, createdName=anminleiryan, createdTime=Fri Apr 07 13:23:05 CST 2023, time=2023-04-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2013933, encodeId=b47f201393305, content=<a href='/topic/show?id=7d69598468' target=_blank style='color:#2F92EE;'>#Dis#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5984, encryptionId=7d69598468, topicName=Dis)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c689267, createdName=cmj8wellington, createdTime=Wed Nov 02 11:23:05 CST 2022, time=2022-11-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2077715, encodeId=939220e7715b7, content=<a href='/topic/show?id=67cc600242' target=_blank style='color:#2F92EE;'>#disorder#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6002, encryptionId=67cc600242, topicName=disorder)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3fc52500170, createdName=12498cbcm00(暂无昵称), createdTime=Sun Nov 20 14:23:05 CST 2022, time=2022-11-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1784531, encodeId=46241e8453135, content=<a href='/topic/show?id=a727600194' target=_blank style='color:#2F92EE;'>#Disord#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6001, encryptionId=a727600194, topicName=Disord)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=aad0444, createdName=cmsvly, createdTime=Tue Feb 07 13:23:05 CST 2023, time=2023-02-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1234804, encodeId=71d712348040d, content=test, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220712/39b2f26c5472459e839fa31189c395a6/b238455e266740099133e1d136de1ff4.png, createdBy=b77a5416288, createdName=天天黑眼圈33, createdTime=Tue Jul 26 09:33:48 CST 2022, time=2022-07-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1471711, encodeId=49b614e1711cb, content=<a href='/topic/show?id=c0132410554' target=_blank style='color:#2F92EE;'>#互作#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=24105, encryptionId=c0132410554, topicName=互作)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dc87121468, createdName=ylz8405, createdTime=Mon Jul 25 14:23:05 CST 2022, time=2022-07-25, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=1738147, encodeId=8da71e381473e, content=<a href='/topic/show?id=e10b600329' target=_blank style='color:#2F92EE;'>#disorders#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6003, encryptionId=e10b600329, topicName=disorders)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=efbf34357637, createdName=ms2186806800017884, createdTime=Tue Dec 27 03:23:05 CST 2022, time=2022-12-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1909341, encodeId=ae9a190934142, content=<a href='/topic/show?id=8039e2512e8' target=_blank style='color:#2F92EE;'>#相互作用#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72512, encryptionId=8039e2512e8, topicName=相互作用)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=hb2008ye, createdTime=Mon Dec 05 18:23:05 CST 2022, time=2022-12-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1878565, encodeId=105e18e8565a1, content=<a href='/topic/show?id=c157696175' target=_blank style='color:#2F92EE;'>#ERS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6961, encryptionId=c157696175, topicName=ERS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e93e105, createdName=anminleiryan, createdTime=Fri Apr 07 13:23:05 CST 2023, time=2023-04-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2013933, encodeId=b47f201393305, content=<a href='/topic/show?id=7d69598468' target=_blank style='color:#2F92EE;'>#Dis#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5984, encryptionId=7d69598468, topicName=Dis)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c689267, createdName=cmj8wellington, createdTime=Wed Nov 02 11:23:05 CST 2022, time=2022-11-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2077715, encodeId=939220e7715b7, content=<a href='/topic/show?id=67cc600242' target=_blank style='color:#2F92EE;'>#disorder#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6002, encryptionId=67cc600242, topicName=disorder)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3fc52500170, createdName=12498cbcm00(暂无昵称), createdTime=Sun Nov 20 14:23:05 CST 2022, time=2022-11-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1784531, encodeId=46241e8453135, content=<a href='/topic/show?id=a727600194' target=_blank style='color:#2F92EE;'>#Disord#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6001, encryptionId=a727600194, topicName=Disord)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=aad0444, createdName=cmsvly, createdTime=Tue Feb 07 13:23:05 CST 2023, time=2023-02-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1234804, encodeId=71d712348040d, content=test, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220712/39b2f26c5472459e839fa31189c395a6/b238455e266740099133e1d136de1ff4.png, createdBy=b77a5416288, createdName=天天黑眼圈33, createdTime=Tue Jul 26 09:33:48 CST 2022, time=2022-07-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1471711, encodeId=49b614e1711cb, content=<a href='/topic/show?id=c0132410554' target=_blank style='color:#2F92EE;'>#互作#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=24105, encryptionId=c0132410554, topicName=互作)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dc87121468, createdName=ylz8405, createdTime=Mon Jul 25 14:23:05 CST 2022, time=2022-07-25, status=1, ipAttribution=)]
    2023-02-07 cmsvly
  7. [GetPortalCommentsPageByObjectIdResponse(id=1738147, encodeId=8da71e381473e, content=<a href='/topic/show?id=e10b600329' target=_blank style='color:#2F92EE;'>#disorders#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6003, encryptionId=e10b600329, topicName=disorders)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=efbf34357637, createdName=ms2186806800017884, createdTime=Tue Dec 27 03:23:05 CST 2022, time=2022-12-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1909341, encodeId=ae9a190934142, content=<a href='/topic/show?id=8039e2512e8' target=_blank style='color:#2F92EE;'>#相互作用#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72512, encryptionId=8039e2512e8, topicName=相互作用)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=hb2008ye, createdTime=Mon Dec 05 18:23:05 CST 2022, time=2022-12-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1878565, encodeId=105e18e8565a1, content=<a href='/topic/show?id=c157696175' target=_blank style='color:#2F92EE;'>#ERS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6961, encryptionId=c157696175, topicName=ERS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e93e105, createdName=anminleiryan, createdTime=Fri Apr 07 13:23:05 CST 2023, time=2023-04-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2013933, encodeId=b47f201393305, content=<a href='/topic/show?id=7d69598468' target=_blank style='color:#2F92EE;'>#Dis#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5984, encryptionId=7d69598468, topicName=Dis)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c689267, createdName=cmj8wellington, createdTime=Wed Nov 02 11:23:05 CST 2022, time=2022-11-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2077715, encodeId=939220e7715b7, content=<a href='/topic/show?id=67cc600242' target=_blank style='color:#2F92EE;'>#disorder#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6002, encryptionId=67cc600242, topicName=disorder)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3fc52500170, createdName=12498cbcm00(暂无昵称), createdTime=Sun Nov 20 14:23:05 CST 2022, time=2022-11-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1784531, encodeId=46241e8453135, content=<a href='/topic/show?id=a727600194' target=_blank style='color:#2F92EE;'>#Disord#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6001, encryptionId=a727600194, topicName=Disord)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=aad0444, createdName=cmsvly, createdTime=Tue Feb 07 13:23:05 CST 2023, time=2023-02-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1234804, encodeId=71d712348040d, content=test, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220712/39b2f26c5472459e839fa31189c395a6/b238455e266740099133e1d136de1ff4.png, createdBy=b77a5416288, createdName=天天黑眼圈33, createdTime=Tue Jul 26 09:33:48 CST 2022, time=2022-07-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1471711, encodeId=49b614e1711cb, content=<a href='/topic/show?id=c0132410554' target=_blank style='color:#2F92EE;'>#互作#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=24105, encryptionId=c0132410554, topicName=互作)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dc87121468, createdName=ylz8405, createdTime=Mon Jul 25 14:23:05 CST 2022, time=2022-07-25, status=1, ipAttribution=)]
    2022-07-26 天天黑眼圈33

    test

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=1738147, encodeId=8da71e381473e, content=<a href='/topic/show?id=e10b600329' target=_blank style='color:#2F92EE;'>#disorders#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6003, encryptionId=e10b600329, topicName=disorders)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=efbf34357637, createdName=ms2186806800017884, createdTime=Tue Dec 27 03:23:05 CST 2022, time=2022-12-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1909341, encodeId=ae9a190934142, content=<a href='/topic/show?id=8039e2512e8' target=_blank style='color:#2F92EE;'>#相互作用#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72512, encryptionId=8039e2512e8, topicName=相互作用)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=hb2008ye, createdTime=Mon Dec 05 18:23:05 CST 2022, time=2022-12-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1878565, encodeId=105e18e8565a1, content=<a href='/topic/show?id=c157696175' target=_blank style='color:#2F92EE;'>#ERS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6961, encryptionId=c157696175, topicName=ERS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e93e105, createdName=anminleiryan, createdTime=Fri Apr 07 13:23:05 CST 2023, time=2023-04-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2013933, encodeId=b47f201393305, content=<a href='/topic/show?id=7d69598468' target=_blank style='color:#2F92EE;'>#Dis#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5984, encryptionId=7d69598468, topicName=Dis)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c689267, createdName=cmj8wellington, createdTime=Wed Nov 02 11:23:05 CST 2022, time=2022-11-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2077715, encodeId=939220e7715b7, content=<a href='/topic/show?id=67cc600242' target=_blank style='color:#2F92EE;'>#disorder#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6002, encryptionId=67cc600242, topicName=disorder)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3fc52500170, createdName=12498cbcm00(暂无昵称), createdTime=Sun Nov 20 14:23:05 CST 2022, time=2022-11-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1784531, encodeId=46241e8453135, content=<a href='/topic/show?id=a727600194' target=_blank style='color:#2F92EE;'>#Disord#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6001, encryptionId=a727600194, topicName=Disord)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=aad0444, createdName=cmsvly, createdTime=Tue Feb 07 13:23:05 CST 2023, time=2023-02-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1234804, encodeId=71d712348040d, content=test, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220712/39b2f26c5472459e839fa31189c395a6/b238455e266740099133e1d136de1ff4.png, createdBy=b77a5416288, createdName=天天黑眼圈33, createdTime=Tue Jul 26 09:33:48 CST 2022, time=2022-07-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1471711, encodeId=49b614e1711cb, content=<a href='/topic/show?id=c0132410554' target=_blank style='color:#2F92EE;'>#互作#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=24105, encryptionId=c0132410554, topicName=互作)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dc87121468, createdName=ylz8405, createdTime=Mon Jul 25 14:23:05 CST 2022, time=2022-07-25, status=1, ipAttribution=)]
    2022-07-25 ylz8405

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