The support of genetic evidence for cardiovascular risk induced by antineoplastic drugs.
The support of genetic evidence for cardiovascular risk induced by antineoplastic drugs.
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抗肿瘤药物诱发心血管风险的遗传证据支持
DOI：
10.1126/sciadv.abb8543
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发表时间：
2020-10
期刊：
影响因子：
13.6
通讯作者：
Li MJ
中科院分区：
文献类型：
--
作者：
Cui H;Zuo S;Liu Z;Liu H;Wang J;You T;Zheng Z;Zhou Y;Qian X;Yao H;Xie L;Liu T;Sham PC;Yu Y;Li MJ
本研究建立了一个遗传证据的纲要，支持抗疟药诱导的心血管风险。心血管功能障碍是长期癌症治疗最常见的并发症之一。越来越多的证据表明，在癌症治疗过程中，抗肿瘤药物会增加心血管风险，严重影响患者生存。然而，人们对与抗抑郁药的心血管风险相关的遗传因素知之甚少。我们建立了一个遗传学证据的纲要，支持非甾体类药物引起的心血管风险。大多数遗传证据归因于改变心血管疾病基因表达的致病等位基因。我们发现，预测会诱发心血管风险的抗肿瘤药物在与心血管不良反应相关的药物中显著富集，包括许多一线癌症治疗药物。功能实验证实，类维生素A X受体激动剂可以减少甘油三酯脂解，从而调节心血管风险。我们的研究结果建立了心血管疾病基因的致病等位基因和药理学调节方向之间的联系，这可能有助于癌症药物的发现和临床试验设计。
The present study establishes a compendium of genetic evidence that support antineoplastic-induced cardiovascular risk. Cardiovascular dysfunction is one of the most common complications of long-term cancer treatment. Growing evidence has shown that antineoplastic drugs can increase cardiovascular risk during cancer therapy, seriously affecting patient survival. However, little is known about the genetic factors associated with the cardiovascular risk of antineoplastic drugs. We established a compendium of genetic evidence that supports cardiovascular risk induced by antineoplastic drugs. Most of this genetic evidence is attributed to causal alleles altering the expression of cardiovascular disease genes. We found that antineoplastic drugs predicted to induce cardiovascular risk are significantly enriched in drugs associated with cardiovascular adverse reactions, including many first-line cancer treatments. Functional experiments validated that retinoid X receptor agonists can reduce triglyceride lipolysis, thus modulating cardiovascular risk. Our results establish a link between the causal allele of cardiovascular disease genes and the direction of pharmacological modulation, which could facilitate cancer drug discovery and clinical trial design.
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影响因子：
17.1
作者：
Finan C;Gaulton A;Kruger FA;Lumbers RT;Shah T;Engmann J;Galver L;Kelley R;Karlsson A;Santos R;Overington JP;Hingorani AD;Casas JP
通讯作者：
Casas JP
遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
影响因子：
14.9
作者：
Buniello, Annalisa;MacArthur, Jacqueline A. L.;Parkinson, Helen
通讯作者：
Parkinson, Helen
影响因子：
51.1
作者：
Cortes, Jorge;Feldman, Eric;Kantarjian, Hagop
通讯作者：
Kantarjian, Hagop
影响因子：
30.8
作者：
Canela-Xandri O;Rawlik K;Tenesa A
通讯作者：
Tenesa A