PLoS Pathog：结核病严重程度受基因影响
越南科学家发现，结核病的严重程度同时受到致病菌和患者的遗传结构的影响。他们希望理解细菌和宿主遗传结构的关系将有助于开发更有效的结核病疗法。他们的研究发表在了上周(3月28日)的《公共科学图书馆·病原学》杂志上。
科学家研究了两组患者的基因变异，其中一组患有非并发的肺结核，另一组患有结核性脑膜炎——后者是一种严重的疾病，当结核菌感染扩散到包围脑和脊髓的膜的时候就会发生。他们还研究了感染患者的结核分枝杆菌的遗传世系。
科学家们发现，拥有免疫系统基因TLR2的特定遗传变异的患者更容易因为一种称为东亚/北京型的结核分枝杆菌菌株而患上结核性脑膜炎。但是欧美世系的结核分枝杆菌导致结核病局限于肺部的可能性更高，这提示它在导致越南人群的结核型脑膜炎方面的能力更低。
牛津大学临床研究组(越南)的威康信托基金会重大海外项目研究员Maxine Caws说，了解病原体和患者遗传结构之间的关系可能解释为什么调查作为风险因素的人类遗传结构变异的研究有时在世界不同的地区表现出不同的结果。
这种易感性可能不仅仅是由于民族遗传差异。她还说，这也可能是由于世界不同地方的结核分枝杆菌种群的遗传差异造成的。
Caws告诉本网站说：“最终，更好地理解人体对病原体的免疫应答可以帮助我们设计更好的全球有效的疫苗，在历史上，这是对抗传染病的最成功方法。”
她还说，尽管北京型菌株常见于亚洲，它在世界许多地区的流行程度正在急速上升，“这更加令人担忧，因为这种结核菌株似乎非常善于获得耐药性。”
生物谷推荐原始出处：
PLoS Pathog 4(3): e1000034. doi:10.1371/journal.ppat.1000034
The Influence of Host and Bacterial Genotype on the Development of Disseminated Disease with Mycobacterium tuberculosis
Abstract
The factors that govern the development of tuberculosis disease are incompletely understood. We hypothesized that some strains of Mycobacterium tuberculosis (M. tuberculosis) are more capable of causing disseminated disease than others and may be associated with polymorphisms in host genes responsible for the innate immune response to infection. We compared the host and bacterial genotype in 187 Vietnamese adults with tuberculous meningitis (TBM) and 237 Vietnamese adults with uncomplicated pulmonary tuberculosis. The host genotype of tuberculosis cases was also compared with the genotype of 392 cord blood controls from the same population. Isolates of M. tuberculosis were genotyped by large sequence polymorphisms. The hosts were defined by polymorphisms in genes encoding Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) and Toll-like receptor-2 (TLR-2). We found a significant protective association between the Euro-American lineage of M. tuberculosis and pulmonary rather than meningeal tuberculosis (Odds ratio (OR) for causing TBM 0.395, 95% confidence intervals (C.I.) 0.193–0.806, P = 0.009), suggesting these strains are less capable of extra-pulmonary dissemination than others in the study population. We also found that individuals with the C allele of TLR-2 T597C allele were more likely to have tuberculosis caused by the East-Asian/Beijing genotype (OR = 1.57 [95% C.I. 1.15–2.15]) than other individuals. The study provides evidence that M. tuberculosis genotype influences clinical disease phenotype and demonstrates, for the first time, a significant interaction between host and bacterial genotypes and the development of tuberculosis.
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