结核分枝杆菌可变数目串联重复序列基因型成簇特征分析

Variable number tandem repeats diversity of Mycobacterium tuberculosis isolates

目的了解广西地区结核分枝杆菌基因型成簇特征及其传播影响因素。方法纳入广西30个结核病耐药监测点2013年登记治疗的痰涂片阳性肺结核患者1 310例，运用可变数目串联重复序列（VNTR）基因分型技术对结核分枝杆菌分离株进行基因分型。统计学处理采用χ2检验，运用非条件Logistic回归分析基因型成簇特征。结果1 310株结核分枝杆菌经VNTR12位点检测分为964个基因型，其中779株为单一基因型，531株可归入185个基因簇之一，每簇含2～40（平均6.6）株分离株。41～60岁成簇比例最高，占45.5%。北京基因型菌株746株，非北京基因型菌株564株，在非北京基因型菌株中原北京菌株占7.4%。结核病近期感染估计值（成簇率）为26.41%；敏感菌株成簇率为24.40%，高于耐药菌株的9.55%（χ2＝23.621，P＝0.000）和耐多药菌株的8.97%（χ2＝9.675，P＝0.002）；北京基因型菌株成簇率为28.69%，高于非北京基因型菌株的23.40%（χ2＝4.610，P＝0.032）。敏感菌株成簇比例为37.43%，高于耐药菌株的14.09%和耐多药菌株的15.38%；北京基因型菌株成簇比例为40.88%，高于非北京基因型菌株的37.77%。结论广西地区结核分枝杆菌基因型具有高度遗传多态性，敏感菌株和北京基因型菌株是广西结核病近期传播的主要流行株。

Objective To investigate the genetic diversity of variable number tandem repeats （VNTR） of Mycobacterium tuberculosis （M. tb） isolates and their impact factors on transmission. Methods A total of 1 310 patients with smear-positive pulmonary tuberculosis registered during 2013 from 30 counties of drug-resistance monitoring sites in Guangxi were enrolled. The VNTR genotyping technique was used to identify and analyze M. tb genotypes. Count data was analyzed by Chi-square test using descriptive statistical method, unconditioned Logistic regression was used to analyze the characteristics of gene clusters. Results A total of 1 310 strains of M. tb were classified into 964 genotypes, of which 779 strains were classified into a single gene cluster, 531 strains were classified into 185 clusters. Each cluster contained 2 to 40 strains （mean 6.6）. Patients aged between 41 and 60 years old had a highest gene cluster proportion （45.5%）. Seven hundred and forty-six strains were Beijing genotype, while 564 were non- Beijing genotype, among which 7. 4% was original Bei]ing genotype. The estimated recent infection （cluster rate） was 26. 41%. The cluster rate was higher in sensitive strains （24.40%） than in drug- resistant strains （9.55%, Z2=23.621, P=0.000） and multi-drug resistant （MDR） strains （8.97%, X2 =9. 675, P=0. 002）, and that was higher in Beijing genotype （28.69%） than Non-Beijing genotype （χ2=23.621,P=0.000）. The clusters proportion in sensitive strain （37.43%） was higher than drug-resistant strains （14.09%） and MDR strains （15. 38%）, and that was higher in Beijing genotype（40.88%） than Non-Beijing genotype （37. 77%）. Conclusions M. tb genetic polymorphisms display highly diversity in Guangxi region. Sensitive strains and Beijing genotype strains are the main epidemic strains.