近日，倫敦國(guó)王學(xué)院等機(jī)構(gòu)研究人員在新一期《細(xì)胞》（Cell）雜志上報(bào)告說(shuō),，在結(jié)核病的治療中,，通常使用抗生素殺滅結(jié)核桿菌，同時(shí)使用地塞米松等藥物來(lái)控制炎癥,，地塞米松藥量是否適當(dāng)對(duì)于治療非常重要,。
如果事先檢測(cè)出結(jié)核病患者的某個(gè)特定基因?qū)儆谀膫€(gè)版本，就可以有針對(duì)性地適當(dāng)用藥,，避免用藥不足導(dǎo)致效果不夠或用藥過(guò)多導(dǎo)致副作用,。
研究人員在分析了數(shù)百名患者的情況后發(fā)現(xiàn)，人體內(nèi)有一個(gè)代號(hào)為L(zhǎng)TA4H的基因,，它有幾個(gè)版本,，而擁有不同版本基因的結(jié)核病患者在治療中所需的地塞米松藥量是不一樣的。有些患者的基因版本會(huì)導(dǎo)致較嚴(yán)重的炎癥，有些則相反,，這就需要因人而異用藥，藥量偏少達(dá)不到治療效果,，而過(guò)量用藥則會(huì)導(dǎo)致一些副作用,。
參與研究的蓋伊·思韋茨說(shuō)，對(duì)基因LTA4H的檢測(cè)是簡(jiǎn)單和快速的,，有助于為患者設(shè)計(jì)最佳治療方案,。此外，由于這個(gè)基因與炎癥之間的關(guān)系在許多疾病中都存在,，這一研究也許還適用于其他疾病的個(gè)性化治療,。（生物谷Bioon.com）
doi:10.1016/j.cell.2011.12.023
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Host Genotype-Specific Therapies Can Optimize the Inflammatory Response to Mycobacterial Infections
David M. Tobin, Francisco J. Roca, Sungwhan F. Oh, Ross McFarland, Thad W. Vickery, John P. Ray, Dennis C. Ko, Yuxia Zou, Nguyen D. Bang, Tran T.H. Chau, Jay C. Vary, Thomas R. Hawn, Sarah J. Dunstan, Jeremy J. Farrar, Guy E. Thwaites, Mary-Claire King, Charles N. Serhan and Lalita Ramakrishnan
Susceptibility to tuberculosis is historically ascribed to an inadequate immune response that fails to control infecting mycobacteria. In zebrafish, we find that susceptibility to Mycobacterium marinum can result from either inadequate or excessive acute inflammation. Modulation of the leukotriene A4 hydrolase (LTA4H) locus, which controls the balance of pro- and anti-inflammatory eicosanoids, reveals two distinct molecular routes to mycobacterial susceptibility converging on dysregulated TNF levels: inadequate inflammation caused by excess lipoxins and hyperinflammation driven by excess leukotriene B4. We identify therapies that specifically target each of these extremes. In humans, we identify a single nucleotide polymorphism in the LTA4H promoter that regulates its transcriptional activity. In tuberculous meningitis, the polymorphism is associated with inflammatory cell recruitment, patient survival and response to adjunctive anti-inflammatory therapy. Together, our findings suggest that host-directed therapies tailored to patient LTA4H genotypes may counter detrimental effects of either extreme of inflammation.
