Associations between human leukocyte antigen class I variants and the Mycobacterium tuberculosis subtypes causing disease.
Associations between human leukocyte antigen class I variants and the Mycobacterium tuberculosis subtypes causing disease.
复制标题
DOI：
10.1093/infdis/jit443
复制
发表时间：
2014-01
期刊：
影响因子：
--
通讯作者：
M. Salie;L. van der Merwe;M. Möller;M. Daya;G. D. van der Spuy;P. V. van Helden;Maureen P. Martin
中科院分区：
文献类型：
--
作者：
M. Salie;L. van der Merwe;M. Möller;M. Daya;G. D. van der Spuy;P. V. van Helden;Maureen P. Martin
背景活动性肺结核的发展是多因素的。宿主和细菌基因型之间的相互作用可能影响疾病结果，一些研究表明结核分枝杆菌菌株对特定人群的适应性。在这里，我们研究人类白细胞抗原（HLA） I类基因在这一生物学过程中的作用。方法对300例南非结核患者HLA I类等位基因进行直接测序分型。采用IS6110限制性内切片段长度多态性基因分型和孢子寡聚分型对结核分枝杆菌进行基因型分型。结果我们发现北京菌株在多次发病的个体中更常见（P < 0.001）， HLA-B27等位基因降低了再次发病的几率（优势比为0.21;P = 0.006）。我们还发现了北京株、LAM株、LCC株和魁北克株引起的特定HLA类型和疾病之间的关联。HLA类型也与来自欧美或东亚谱系的菌株引起的疾病有关，这些等位基因在其同域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。结论：这是人类HLA分型与结核分枝杆菌基因型相关性的首次报道，强调在研究结核病的发展时需要同时考虑宿主和病原体遗传学。
BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.