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Nat Commun:遗传突变会影响他汀类药物效应

2014-11-03 佚名 生物谷

近日,刊登在国际杂志Nature Communications上的一篇研究报告中,来自伦敦女王大学的科学家们通过对4万名进行他汀类药物治疗的患者的大型分析研究后鉴别出了两种新型的遗传突变,这两种遗传突变可以影响机体坏胆固醇对他汀类疗法的反应。 他汀类药物是临床中广泛使用的用于降低坏胆固醇的药物,其可将坏胆固醇水平降低至55%,从而可以有效减少心脏病的风险,尽管如此,不同病人对他汀类药物的

近日,刊登在国际杂志Nature Communications上的一篇研究报告中,来自伦敦女王大学的科学家们通过对4万名进行他汀类药物治疗的患者的大型分析研究后鉴别出了两种新型的遗传突变,这两种遗传突变可以影响机体坏胆固醇对他汀类疗法的反应。

他汀类药物是临床中广泛使用的用于降低坏胆固醇的药物,其可将坏胆固醇水平降低至55%,从而可以有效减少心脏病的风险,尽管如此,不同病人对他汀类药物的反应也并不一样。这项研究中研究人员对6组随机临床数据及10组观察性研究进行分析来寻找影响病人对他汀类药物反应的遗传突变,结果研究者发现了2种常见的遗传突变,该遗传突变可以明显影响他汀类疗法期间患者机体坏胆固醇降低水平的等级。

Mark Caulfield教授说道,这项研究可以帮助我们理解遗传突变影响患者对他汀类疗法反应的分子机制,我们发现个体中对他汀类反应的差异中,4种相关的遗传突变产生的效应仅占到了5%,其中一种已经鉴别的遗传突变可以增强个体对他汀类药物的反应,而第二种突变则可以帮助肝脏吸收他汀类药物,降低药物的反应。

目前他汀类药物是最安全有效的临床用药,尽管其利用了相同的靶点,但是在不同群体中某些他汀类药物更加有效;本文研究阐述了相互影响基因的网络或许可以影响他汀类药物对机体的反应,未来或许可以帮助科学家们针对不同病人选择更加有效的他汀类药物。

原始出处:

Postmus I1, Trompet S2, Deshmukh HA3, Barnes MR4, Li X5, Warren HR6, Chasman DI7, Zhou K3, Arsenault BJ8, Donnelly LA3, Wiggins KL9, Avery CL10, Griffin P11, Feng Q12, Taylor KD5, Li G9, Evans DS13, Smith AV14, de Keyser CE15, Johnson AD16, de Craen AJ1, Stott DJ17, Buckley BM18, Ford I19, Westendorp RG20, Eline Slagboom P21, Sattar N22, Munroe PB6, Sever P23, Poulter N23, Stanton A24, Shields DC25, O'Brien E26, Shaw-Hawkins S4, Ida Chen YD5, Nickerson DA27, Smith JD27, Pierre Dubé M8, Matthijs Boekholdt S28, Kees Hovingh G29, Kastelein JJ29, McKeigue PM30, Betteridge J, Neil A31, Durrington PN32, Doney A3, Carr F3, Morris A3, McCarthy MI33, Groop L34, Ahlqvist E34; Welcome Trust Case Control Consortium, Bis JC9, Rice K35, Smith NL36, Lumley T37, Whitsel EA38, Stürmer T10, Boerwinkle E39, Ngwa JS11, O'Donnell CJ40, Vasan RS41, Wei WQ42, Wilke RA43, Liu CT11, Sun F11, Guo X5, Heckbert SR44, Post W45, Sotoodehnia N46, Arnold AM35, Stafford JM47, Ding J48, Herrington DM49, Kritchevsky SB50, Eiriksdottir G51, Launer LJ52, Harris TB52, Chu AY53, Giulianini F53, MacFadyen JG53, Barratt BJ54, Nyberg F55, Stricker BH56, Uitterlinden AG57, Hofman A58, Rivadeneira F59, Emilsson V51, Franco OH60, Ridker PM53, Gudnason V14, Liu Y48, Denny JC61, Ballantyne CM62, Rotter JI5, Adrienne Cupples L63, Psaty BM64, Palmer CN3, Tardif JC8, Colhoun HM65, Hitman G66, Krauss RM67, Wouter Jukema J68, Caulfield MJ6; Membership of Wellcome Trust Case Control Consortium; Data and Analysis Group; DNA, Genotyping, Data QC and Informatics Group; Publications Committee; Membership of Wellcome Trust Case Control Consortium; Data and Analysis Group; DNA Genotyping Data QC and Informatics Group; Publications Committee.Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.Nat Commun. 2014 Oct 28;5:5068. doi: 10.1038/ncomms6068.

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    2014-11-07 liye789132251
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    2014-12-28 liuli5079

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大量研究奠定了他汀类药物在心血管疾病防治中不可动摇的地位。他汀类药物具有良好的耐受性,不良反应少,对肝脏和肌肉潜在的不良反应已得到医患重视。2012年2月29日,美国食品药物管理局(FDA)的官方网站上又发布了有关他汀类药物说明书需修改的告示,包括他汀的肝酶监测、药物相互作用、神经系统不良反应、血糖异常和新发糖尿病,以及以往关于肿瘤安全性的争议再次引起人们对他汀类药物的安全性问题的关注。重新认

BMJ:NICE他汀类药物指南应公布需治疗人数及治疗风险

当以需治疗人数(NNT)作为评估他汀获益指标,而非ASCOT-LLA研究中所呈现的他汀治疗可以减少36%心血管疾病发生风险为参照时,他汀获益或许远非如此巨大。英国医学杂志应该质疑目前宣称的他汀治疗益处及其最小化的副作用。英国国家健康临床优化研究院(NICE)发布的指南草案影响力很大,因此必须准确而又通俗易懂地描述指南证据。明确的指南有助于全科医生等采用最佳基于证据的建议规劝患者服药。出于明确性和完

NEJM:他汀类药或不能改善脓毒症并ARDS 者预后

急性呼吸窘迫综合征(ARDS)中,肺部和其他器官炎症可导致危及生命的 。羟甲基戊二酰辅酶A还原酶抑制剂(他汀类药物)可调节炎症反应。有观察性研究提示,他汀类药物可改善脓毒症患者临床转归。但美国国立心肺血液研究所学者所进行的一项研究提示,瑞舒伐他汀不能改善脓毒症合并ARDS患者的临床转归。文章发表于2014年5月18日的NEJM上。该随机双盲安慰剂对照多中心临床试验预期纳入1000名脓毒症合并ARD

JACC:他汀类药物可降低无心血管病史患者中风与心梗风险

森林图:心肌梗塞与中风在他汀类药物和安慰剂组中风险比较 非心源性死亡和心源性死亡在他汀类药物和安慰剂组中风险比较 新生肿瘤在他汀类药物和安慰剂组中风险比较 研究要点: 1.与年轻人相比,81%的心血管源性死亡在65岁以上老年群体中。目前的指南推荐,既往有心血管病史的老年患者(年龄不低于65岁)应使用他汀类药物,而对于既往无心血管病史的老年人来说,临床指南并不支持使用

AAOS 2014:他汀类药物或可降低关节置换术后的血栓风险

长期以来,人们对他汀类药物的认识即为降低胆固醇药物,但最近,有研究发现,在非手术健康患者中,该类药物可减低深静脉血栓形成的发生风险。在3月11日的2014 美国骨外科学会(AAOS)年会上,研究者首次汇报了一项新研究,该研究显示,他汀类药物与常规血栓预防治疗联用可显著降低全关节置换(TJR)术后患者深静脉血栓形成(VTE)事件的发生风险,这项研究是相关领域进行的第一项研究。

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