近日，伦敦国王学院等机构研究人员在新一期《细胞》（Cell）杂志上报告说，在结核病的治疗中，通常使用抗生素杀灭结核杆菌，同时使用地塞米松等药物来控制炎症，地塞米松药量是否适当对于治疗非常重要。
如果事先检测出结核病患者的某个特定基因属于哪个版本，就可以有针对性地适当用药，避免用药不足导致效果不够或用药过多导致副作用。
研究人员在分析了数百名患者的情况后发现，人体内有一个代号为LTA4H的基因，它有几个版本，而拥有不同版本基因的结核病患者在治疗中所需的地塞米松药量是不一样的。有些患者的基因版本会导致较严重的炎症，有些则相反，这就需要因人而异用药，药量偏少达不到治疗效果，而过量用药则会导致一些副作用。
参与研究的盖伊·思韦茨说，对基因LTA4H的检测是简单和快速的，有助于为患者设计最佳治疗方案。此外，由于这个基因与炎症之间的关系在许多疾病中都存在，这一研究也许还适用于其他疾病的个性化治疗。（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.
