不同可变数目串联重复序列组合对中国流行结核分枝杆菌分辨力的评价研究

Discriminatory Power of Variable Number on Tandem Repeats Loci for Genotyping Mycobacterium tuberculosis Strains in China

目的在规范化的结核分枝杆菌（Mycobacteriumtuberculosis，MTB）可变数目串联重复序列（variablenumberoftandemrepeats，VNTR）基因分型的基础上，构建我国31个省（自治区、直辖市）VNTR数据库，每个省优化一套VNTR位点组合，为我国结核病预防控制策略的制定提供科学依据。方法对2007—2008年全国结核病耐药性基线调查的4116株MTBl5位点VNTR（15-VNTR）基因分型。汉高指数（Hunter-GastonIndex，HGI）分析每个位点的分辨率。依据谱系流行特征，以分辨率高和稳定性强为原则，为各省设计一套VNTR优化组合（12．VNTR、10．VNTR、8-VNTR和5-VNTR），采用HGI和成簇率进行评价。结果完成了涵盖率为96．36％（3966／4116）MTB完整15-VNTR图谱。发现QUB11b、MIRU26等7个高分辨率位点；QUB26、MIRU16、Mtub21、QUB11b在部分地区遗传稳定性差。内蒙古自治区、重庆市、黑龙江省的最优组合为10．VNTR，其他各省的最佳组合为8-VNTR。结论VNTR数据库的建立将推动全国范围MTB传染源的追踪；各省优化VNTR组合的推出有助于当地结核病疫情的监测和群体遗传学的研究。

Objective Using the standard genotype method, variable number of tandem repeats （VNTR）, we constructed a VNTR database to cover all provinces and proposed a set of optimized VNTR loci combinations for each province, in order to improve the preventive and control programs on tuberculosis, in China. Methods A total of 15 loci VNTR was used to analyze 4116 Mycobacterium tuberculosis strains, isolated from national survey of Drug Resistant Tuberculosis, in 2007. Hunter-Gaston Index （HGI） was also used to analyze the discriminatory power of each VNTR site. A set combination of 12-VNTR, 10-VNTR, 8-VNTR and 5-VNTR was respectively constructed for each province, based on 1） epidemic characteristics of M. tuberculosis lineages in China, with high discriminatory power and genetic stability. Results Through the completed 15 loci VNTR patterns of 3966 strains under 96.36% （3966/4116） coverage, we found seven high HGI loci （including QUBllb and MIRU26） as well as low stable loci （including QUB26, MIRU16, Mtub21 and QUBllb） in several areas. In all the 31 provinces, we found an optimization VNTR combination as 10-VNTR loci in Inner Mongolia, Chongqing and Heilongjiang, but with 8-VNTR combination shared in other provinces. Conclusions It is necessary to not only use the VNTR database for tracing the source of infection and cluster of M. tuberculosis in the nation but also using the set of optimized VNTR combinations in monitoring those local epidemics and M. tuberculosis （genetics in local） population.