Interaction analysis of Mycobacterium tuberculosis between the host environment and highly mutated genes from population genetic structure comparison.
Interaction analysis of Mycobacterium tuberculosis between the host environment and highly mutated genes from population genetic structure comparison.
复制标题
从群体遗传结构比较分析结核分枝杆菌宿主环境与高突变基因的相互作用
DOI：
10.1097/md.0000000000027125
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发表时间：
2021-09-03
期刊：
影响因子：
1.6
通讯作者：
Huang L
中科院分区：
文献类型：
--
作者：
Cui Z;Liu J;Chang Y;Lin D;Luo D;Ou J;Huang L
摘要我们的目的是研究观察到的结核分枝杆菌（M. tb）基因组变异在寒冷和炎热地区均匀分布的地区之间的遗传和人口统计学差异和相互作用。根据过去5年报告的结核病发病率确定了冷热点地区。291 M进行全基因组测序。2018年1月至6月期间的结核分离株。应用分子方差分析和多因素降维模型检测基因-基因-环境相互作用。使用多变量logistic回归模型计算校正优势比（OR）和95%置信区间（CI），以检验基因突变对结核病流行的影响程度。热点地区北京家庭品系比例显著高于冷区(64.63% vs 50.69%, P =；022)，在老年人、低BMI人群和有结核病患者接触史的人群中（均P < 0.05）。来自寒区的个体出外旅游频率较高（P < 0.05）。Rv1186c、Rv3900c、Rv1508c、Rv0210和一个基因间区（SNP位点：3847237）的突变在冷热区表现出显著差异。（p < 0.001）。MDR模型显示年龄层与BMI（交互熵：−3.55%）和Rv0210突变（交互熵：−2.39%）之间存在明显的负交互效应。通过Rv0210的突变，BMI与Rv0210具有较低的独立效应（互作熵为- 1.46%）。我们的数据表明，年龄、BMI和Rv0210基因多态性在结核分枝杆菌的传播和发展中具有统计学意义。该结果为不同人群结核分枝杆菌的易感基因研究提供了线索。特征菌株表现为局部流行。加强各地区菌株基因型监测可作为疫情外溢的早期预警信号。
Supplemental Digital Content is available in the text Abstract We aimed to investigate the genetic and demographic differences and interactions between areas where observed genomic variations in Mycobacterium tuberculosis (M. tb) were distributed uniformly in cold and hot spots. The cold and hot spot areas were identified using the reported incidence of TB over the previous 5 years. Whole genome sequencing was performed on 291 M. tb isolates between January and June 2018. Analysis of molecular variance and a multifactor dimensionality reduction (MDR) model was applied to test gene-gene-environment interactions. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were computed to test the extent to which genetic mutation affects the TB epidemic using a multivariate logistic regression model. The percentage of the Beijing family strain in hot spots was significantly higher than that in cold spots (64.63% vs 50.69%, P = .022), among the elderly, people with a low BMI, and those having a history of contact with a TB patient (all P < .05). Individuals from cold spot areas had a higher frequency of out-of-town traveling (P < .05). The mutation of Rv1186c, Rv3900c, Rv1508c, Rv0210, and an Intergenic Region (SNP site: 3847237) showed a significant difference between cold and hot spots. (P < .001). The MDR model displayed a clear negative interaction effect of age groups with BMI (interaction entropy: −3.55%) and mutation of Rv0210 (interaction entropy: −2.39%). Through the mutations of Rv0210 and BMI had a low independent effect (interaction entropy: −1.46%). Our data suggests a statistically significant role of age, BMI and the polymorphisms of Rv0210 genes in the transmission and development of M. tb. The results provide clues for the study of susceptibility genes of M. tb in different populations. The characteristic strains showed a local epidemic. Strengthening genotype monitoring of strains in various regions can be used as an early warning signal of epidemic spillover.