Genetics and pharmacogenetics of the leukotriene pathway.
Genetics and pharmacogenetics of the leukotriene pathway.
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DOI：
10.1016/j.jaci.2009.06.035
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发表时间：
2009-09
影响因子：
14.2
通讯作者：
Drazen, Jeffrey M.
中科院分区：
文献类型：
--
作者：
Tantisira, Kelan G.;Drazen, Jeffrey M.
关键词：
白三烯现在是哮喘炎症过程的公认贡献者，白三烯修饰剂是哮喘治疗的中流砥柱。本文综述了白三烯途径基因在哮喘发病机制和治疗反应中作用的相关研究，特别是与哮喘影响状态、阿司匹林加重呼吸道疾病的发生和药物遗传反应相关的基因变异。虽然已发表的研究受到样本量小和缺乏独立复制的限制，但多个白三烯途径基因中的多个位点现在已在多个与哮喘或哮喘治疗反应有关的研究中相关。这些特定的变种包括ALOX5的两个变种，它们都与5-LO抑制和白三烯受体拮抗剂的反应有关，两个已建立的半胱氨酰白三烯受体拮抗剂的变种，CySLTR1和CySLTR2都与至少两个独立人群的哮喘易感性有关，以及LTC4S启动子的多态，与哮喘的病情和哮喘加重的呼吸系统疾病有关。尽管取得了这些成功，但对这一途径的遗传学研究仍处于形成阶段。未来的研究需要通过增加样本量和全基因组方法来提供更广泛的调查范围。
Leukotrienes are now established contributors to the inflammatory process in asthma and leukotriene modifiers are mainstays in the therapy of asthma. This review focuses on published association studies implicating the role of leukotriene pathway genes in asthma pathogenesis and treatment response, specifically focusing on those genetic variants associated with asthma affection status, the development of aspirin exacerbated respiratory disease, and pharmacogenetic response. While published studies have been limited by small sample sizes and lack of independent replication, multiple loci within multiple leukotriene pathway genes have now been associated in more than one study related to asthma or asthma treatment response. Those specific variants include two variants in ALOX5 that are both associated with response to 5-LO inhibition and to leukotriene receptor antagonists, variants in the two established cysteinyl leukotriene receptor antagonists, CYSLTR1 and CYSLTR2 that are both associated with asthma susceptibility in at least two independent populations, and a LTC4S promoter polymorphism that has been associated with asthma affection status and with asthma exacerbated respiratory disease. Desite these successes, genetic investigations into this pathway remain in their formative stages. Future studies aimed at providing a broader scope of investigation through increased sample sizes and through genome-wide approaches are needed.
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影响因子：
6.7
作者：
Drazen, JM;Silverman, EK;Lee, TH
通讯作者：
Lee, TH
影响因子：
14.2
作者：
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通讯作者：
Akiyama, K
影响因子：
24.3
作者：
Hong, X.;Zhou, H.;Xu, X.
通讯作者：
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影响因子：
12.4
作者：
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通讯作者：
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影响因子：
4.3
作者：
Telleria, Juan J.;Blanco-Quiros, Alfredo;Diez, Ignacio
通讯作者：
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