MRC Centre for Molecular and Cellular Biology and the DST/NRF Centre of Excellence for Biomedical TB Research, Division of Molecular Biology and Human Genetics, Stellenbosch University, Tygerberg.
J Infect Dis. 2014 Jan 15;209(2):216-23. doi: 10.1093/infdis/jit443. Epub 2013 Aug 14.
The development of active tuberculosis disease has been shown to be multifactorial. Interactions between host and bacterial genotype may influence disease outcome, with some studies indicating the adaptation of M. tuberculosis strains to specific human populations. Here we investigate the role of the human leukocyte antigen (HLA) class I genes in this biological process.
Three hundred patients with tuberculosis from South Africa were typed for their HLA class I alleles by direct sequencing. Mycobacterium tuberculosis genotype classification was done by IS6110 restriction fragment length polymorphism genotyping and spoligotyping.
We showed that Beijing strain occurred more frequently in individuals with multiple disease episodes (P < .001) with the HLA-B27 allele lowering the odds of having an additional episode (odds ratio, 0.21; P = .006). Associations were also identified for specific HLA types and disease caused by the Beijing, LAM, LCC, and Quebec strains. HLA types were also associated with disease caused by strains from the Euro-American or East Asian lineages, and the frequencies of these alleles in their sympatric human populations identified potential coevolutionary events between host and pathogen.
This is the first report of the association of human HLA types and M. tuberculosis strain genotype, highlighting that both host and pathogen genetics need to be taken into consideration when studying tuberculosis disease development.
活动性结核病的发展是多因素的。宿主和细菌基因型之间的相互作用可能影响疾病结局，一些研究表明结核分枝杆菌菌株适应特定的人类群体。在这里，我们研究了人类白细胞抗原（HLA）I 类基因在这一生物学过程中的作用。
我们通过直接测序对来自南非的 300 名结核病患者进行 HLA I 类等位基因分型。通过 IS6110 限制片段长度多态性基因分型和 spoligotyping 对结核分枝杆菌基因型进行分类。
我们表明，北京菌株在多次发病的个体中更为常见（P <.001），HLA-B27 等位基因降低了再次发病的几率（比值比，0.21；P =.006）。还发现了特定 HLA 类型与北京、LAM、LCC 和魁北克菌株引起的疾病之间的关联。HLA 类型也与来自欧美或东亚谱系的菌株引起的疾病有关，这些等位基因在其共生人群中的频率确定了宿主和病原体之间潜在的共同进化事件。
这是首次报道人类 HLA 类型与结核分枝杆菌菌株基因型的关联，强调在研究结核病发展时需要考虑宿主和病原体的遗传学。
