Pharmacogenetics and the development of personalized approaches for combination therapy in asthma.
Pharmacogenetics and the development of personalized approaches for combination therapy in asthma.
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DOI：
10.1007/s11882-013-0372-x
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发表时间：
2013-10
影响因子：
5.5
通讯作者：
Ortega, Victor E.
中科院分区：
文献类型：
--
作者：
Miller, Stacey M.;Ortega, Victor E.
哮喘是一种常见的慢性呼吸道疾病，可以采用不同的治疗方法进行治疗。LABA和ICS治疗的组合产生协同相互作用，可有效改善哮喘症状控制;然而，遗传变异有可能改变疗效。两种药物均介导由基因变异组成的复杂分子途径，已通过分析β2-肾上腺素能受体和糖皮质激素途径中的候选基因进行了研究。这些药物遗传学研究仅限于临床试验队列的回顾性分析和少量前瞻性、基因型分层试验。最近，全基因组关联研究结合其他队列中的复制和体外细胞模型已用于鉴定新的途径相关药物遗传学变异。本文综述了β2-肾上腺素能受体和糖皮质激素途径的药物遗传学，强调了相互作用途径中多个基因变异的基因型效应，这些基因变异可能导致对吸入性β受体激动剂和糖皮质激素的不同反应。随着我们对这些遗传机制的理解的提高，可能会开发出一系列生物标志物来确定哪种联合疗法对个体哮喘患者最有效，风险最小。在我们能够迎来哮喘的个性化医学时代之前，首先重要的是提高我们使用研究设计，分析方法和体外功能研究相结合来分析大型临床试验队列中大量遗传数据的能力。
Asthma is a common, chronic disease of the airways that is treated with a combination of different therapies. The combination of LABA and ICS therapy results in a synergistic interaction that is efficacious in improving asthma symptom control; however, genetic variation has the potential to alter therapeutic efficacy. Both agents mediate complex molecular pathways consisting of gene variation that has been investigated with the analysis of candidate genes in the β2-adrenergic receptor and glucocorticoid pathway. These pharmacogenetic studies have been limited to retrospective analyses of clinical trial cohorts and a small number of prospective, genotype-stratified trials. More recently, genome-wide association studies in combination with replication in additional cohorts and in vitro cell-based models have been used to identify novel pathway-related pharmacogenetic variations. This review of the pharmacogenetics of the β2-adrenergic receptor and glucocorticoid pathways highlights the genotypic effects of variation in multiple genes from interacting pathways which may contribute to differential responses to inhaled beta agonists and glucocorticoids. As our understanding of these genetic mechanisms improves, panels of biomarkers may be developed to determine which combination therapies are the most effective with the least risk to an individual asthma patient. Before we can usher in an era of personalized medicine for asthma, it is first important to improve our ability to analyze large volumes of genetic data in large clinical trial cohorts using a combination of study designs, analytical methods, and in vitro functional studies.
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影响因子：
4.5
作者：
Himes BE;Jiang X;Hu R;Wu AC;Lasky-Su JA;Klanderman BJ;Ziniti J;Senter-Sylvia J;Lima JJ;Irvin CG;Peters SP;Meyers DA;Bleecker ER;Kubo M;Tamari M;Nakamura Y;Szefler SJ;Lemanske RF Jr;Zeiger RS;Strunk RC;Martinez FD;Hanrahan JP;Koppelman GH;Postma DS;Nieuwenhuis MA;Vonk JM;Panettieri RA Jr;Markezich A;Israel E;Carey VJ;Tantisira KG;Litonjua AA;Lu Q;Weiss ST
通讯作者：
Weiss ST
影响因子：
64.8
作者：
Frazer, Kelly A.;Ballinger, Dennis G.;Cox, David R.;Hinds, David A.;Stuve, Laura L.;Gibbs, Richard A.;Belmont, John W.;Boudreau, Andrew;Hardenbol, Paul;Leal, Suzanne M.;Pasternak, Shiran;Wheeler, David A.;Willis, Thomas D.;Yu, Fuli;Yang, Huanming;Zeng, Changqing;Gao, Yang;Hu, Haoran;Hu, Weitao;Li, Chaohua;Lin, Wei;Liu, Siqi;Pan, Hao;Tang, Xiaoli;Wang, Jian;Wang, Wei;Yu, Jun;Zhang, Bo;Zhang, Qingrun;Zhao, Hongbin;Zhao, Hui;Zhou, Jun;Gabriel, Stacey B.;Barry, Rachel;Blumenstiel, Brendan;Camargo, Amy;Defelice, Matthew;Faggart, Maura;Goyette, Mary;Gupta, Supriya;Moore, Jamie;Nguyen, Huy;Onofrio, Robert C.;Parkin, Melissa;Roy, Jessica;Stahl, Erich;Winchester, Ellen;Ziaugra, Liuda;Altshuler, David;Shen, Yan;Yao, Zhijian;Huang, Wei;Chu, Xun;He, Yungang;Jin, Li;Liu, Yangfan;Shen, Yayun;Sun, Weiwei;Wang, Haifeng;Wang, Yi;Wang, Ying;Xiong, Xiaoyan;Xu, Liang;Waye, Mary M. Y.;Tsui, Stephen K. W.;Wong, J. Tze-Fei;Galver, Luana M.;Fan, Jian-Bing;Gunderson, Kevin;Murray, Sarah S.;Oliphant, Arnold R.;Chee, Mark S.;Montpetit, Alexandre;Chagnon, Fanny;Ferretti, Vincent;Leboeuf, Martin;Olivier, Jean-Franccois;Phillips, Michael S.;Roumy, Stephanie;Sallee, Clementine;Verner, Andrei;Hudson, Thomas J.;Kwok, Pui-Yan;Cai, Dongmei;Koboldt, Daniel C.;Miller, Raymond D.;Pawlikowska, Ludmila;Taillon-Miller, Patricia;Xiao, Ming;Tsui, Lap-Chee;Mak, William;Song, You Qiang;Tam, Paul K. H.;Nakamura, Yusuke;Kawaguchi, Takahisa;Kitamoto, Takuya;Morizono, Takashi;Nagashima, Atsushi;Ohnishi, Yozo;Sekine, Akihiro;Tanaka, Toshihiro;Tsunoda, Tatsuhiko;Deloukas, Panos;Bird, Christine P.;Delgado, Marcos;Dermitzakis, Emmanouil T.;Gwilliam, Rhian;Hunt, Sarah;Morrison, Jonathan;Powell, Don;Stranger, Barbara E.;Whittaker, Pamela;Bentley, David R.;Daly, Mark J.;de Bakker, Paul I. W.;Barrett, Jeff;Chretien, Yves R.;Maller, Julian;McCarroll, Steve;Patterson, Nick;Pe'er, Itsik;Price, Alkes;Purcell, Shaun;Richter, Daniel J.;Sabeti, Pardis;Saxena, Richa;Schaffner, Stephen F.;Sham, Pak C.;Varilly, Patrick;Altshuler, David;Stein, Lincoln D.;Krishnan, Lalitha;Smith, Albert Vernon;Tello-Ruiz, Marcela K.;Thorisson, Gudmundur A.;Chakravarti, Aravinda;Chen, Peter E.;Cutler, David J.;Kashuk, Carl S.;Lin, Shin;Abecasis, Goncalo R.;Guan, Weihua;Li, Yun;Munro, Heather M.;Qin, Zhaohui Steve;Thomas, Daryl J.;McVean, Gilean;Auton, Adam;Bottolo, Leonardo;Cardin, Niall;Eyheramendy, Susana;Freeman, Colin;Marchini, Jonathan;Myers, Simon;Spencer, Chris;Stephens, Matthew;Donnelly, Peter;Cardon, Lon R.;Clarke, Geraldine;Evans, David M.;Morris, Andrew P.;Weir, Bruce S.;Tsunoda, Tatsuhiko;Johnson, Todd A.;Mullikin, James C.;Sherry, Stephen T.;Feolo, Michael;Skol, Andrew
通讯作者：
Skol, Andrew
影响因子：
6.7
作者：
Drazen, JM;Silverman, EK;Lee, TH
通讯作者：
Lee, TH
影响因子：
10
作者：
GRAINGER, J;WOODMAN, K;BEASLEY, R
通讯作者：
BEASLEY, R
影响因子：
2.9
作者：
GREEN, SA;TURKI, J;LIGGETT, SB
通讯作者：
LIGGETT, SB