A polymorphism in the inducible nitric oxide synthase gene is associated with tuberculosis
A polymorphism in the inducible nitric oxide synthase gene is associated with tuberculosis
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DOI：
10.1016/j.tube.2007.03.002
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发表时间：
2007-07-01
期刊：
影响因子：
3.2
通讯作者：
Martin, Javier
中科院分区：
文献类型：
--
作者：
Gomez, Luis Miguel;Anaya, Juan-Manuel;Martin, Javier
iNOS或NOS 2是一种在广谱感染因子的免疫控制中起关键作用的分子。研究受到难以估计体内一氧化氮（NO）产生的阻碍，但遗传学研究提供了一种潜在的手段，检查NO产生和疾病结果之间的关系。为了更好地表征决定结核病易感性的宿主遗传因素，我们评估了NOS 2A基因的两种多态性对哥伦比亚西北部人群（中度高发流行区）发生肺结核风险的影响。对114例人类免疫缺陷病毒阴性的结核病患者和304例健康对照者进行了NOS 2A CCTTT和TAAA多态性检测。160名健康对照者进行结核菌素皮肤试验。分析显示，具有NOS 2A CCTTT多态性的患者和对照组之间存在显著差异（P = 0.0001，Pc = 0.001，OR = 0.4，95%CI = 0.3-0.7），与TST状态无关。将NOS 2A等位基因分为短重复（8-11）和长重复（12-16）两种类型，结核病组与对照组相比，短重复的差异有统计学意义（P = 0.005，OR = 0.63，95% CI = 0.46-0.86）。未检测到与NOS 2A TAAA的个体相关性。这些结果表明，NOS 2A基因的多态性影响结核病的易感性，并建议在分枝杆菌感染的发病机制中的NOS 2A的作用。(c)2007爱思唯尔有限公司保留所有权利。
iNOS or NOS2 is a molecule that plays a key role in the immunological control of a broad spectrum of infectious agents. Investigation is hampered by difficulty in estimating in vivo production of nitric oxide (NO), but genetic studies provide a potential means of examining the relation between NO production and disease outcome. To better characterize the host genetic factors determining the susceptibility to TB, we evaluated the influence of two polymorphisms in the NOS2A gene on the risk of developing pulmonary TB in a Northwestern Colombian population, which is a moderately-high endemic area. One hundred and fourteen patients with TB and negative for human immunodeficiency virus, plus 304 healthy controls were examined for NOS2A CCTTT and TAAA polymorphisms. A total of 160 healthy controls mentioned before, underwent tuberculin skin test (TST). Analysis disclosed significant differences between patients and controls with NOS2A CCTTT polymorphism (P = 0.0001, Pc = 0.001, OR = 0.4, and 95%Cl = 0.3-0.7) independent of TST status. When the NOS2A alleles were stratified into short (8-11) and long (12-16) repeats, significant differences with short repeats were observed between TB patients and all controls (P = 0.005, OR = 0.63, 95% Cl = 0.46-0.86). No individual association with NOS2A TAAA was detected. These results indicate that a polymorphism in the NOS2A gene influences the susceptibility to TB and suggest a role for NOS2A in the pathogenesis of mycobacterial infection. (c) 2007 Elsevier Ltd. All rights reserved.