广东省地区结核分枝杆菌寡核苷酸基因分型及耐药相关性

Genotyping and drug resistance analysis of Mycobacterium tuberculosis from Guangdong area,China

目的研究结核分枝杆菌(MTB)不同基因型在广东省各地区的流行情况及其耐药相关性。方法随机数字法抽取广州市胸科医院2014-2015年临床分离的来自于广东省不同地区的504株结核分枝杆菌菌株,采用比例法进行药物敏感性实验,选用间隔区寡核苷酸分型方法(Spoligotyping)对结核分枝杆菌进行基因分型。基因型耐药率差异比较采用χ2检验。结果 (1)在504株结核分枝杆菌临床分离株中北京家族和非北京家族分别是386株和118株。非北京家族中,T家族高达48株;其余是H3家族、EAI家族、MANU家族、AMBIGO家族、LAM家族以及新发基因型。北京家族构成比在性别、年龄上无统计学差异(P>0.05),但在汕头、汕尾、揭阳、东莞四个地级市的构成比低于广州市,差异有统计学意义(P<0.05)。(2)504株结核分枝杆菌中,453株在SPOIDB 4.0数据库中分为49种寡核苷酸类型归类于30个簇,其主要流行簇依次为:SIT1、SIT53、SIT52、SIT19、SIT523。SIT1基因型的异烟肼(INH)、利福平(RFP)、链霉素(SM)、乙胺丁醇(EMB)、吡嗪酰胺(PZA)、阿米卡星(AMK)、左氧氟沙星(LVFX)、耐多药(MDR)、泛耐药(XDR)的耐药率均高于SIT53、SIT52、SIT19,而SIT523在RFP、SM、EMB、MDR的耐药率方面高于SIT1(3)主要流行基因型北京家族的INH、PZA、AMK的耐药率高于非北京家族,差异有统计学意义(P<0.05),其余药物的耐药性无显著性差异(P>0.05)。结论广东省结核分枝杆菌呈基因多态性,北京基因型菌株为本省结核分枝杆菌主要流行株,而且与异烟肼、吡嗪酰胺、阿米卡星耐药相关。非北京基因型在潮汕和东莞等华侨之乡比例有所增加。

We studied the prevalence and drug resistance of different genotypes of Mycobacterium tuberculosis （MTB） in various regions of Guangdong Province. A total of 504 clinical isolates were collected by Guangzhou Chest Hospital in Guangdong from 2014 to 2015, China. Proportional method for drug sensitivity test, and spoligotyping was chosen to genotyping of these MTB. Differences in genotype resistance rates were compared using the Chi-square test. Results showed that： （1）Among the 504 isolates of MTB, 386 strains were in Beijing families and 118 were non-Beijing families. Among the Non-beijing family, T family was up to 48. The rest were H3 family, EAI family, MANU family, AMBIGO family, LAM family and new genotype. There was no significant difference in gender and age between constituent ratios of Beijing family （P〉0.05）, but the constituent ratios in four prefecture-level cities in Shantou, Shanwei, Jieyang and Dongguan were lower than those in Guangzhou, with a significant difference （P〈0.05）.（2） Among the 504 isolates of MTB, 453 strains were divided into 49 types of oligonucleotide and classified as 30 clusters in SPOIDB 4.0 databas,The main popular clusters were： SIT1, SIT53, SIT52, SIT19, SIT523. The resistance rates of Isoniazid （INH）, rifampicin （RFP）, streptomycin （SM）, ethambutol （EMB）, pyrazinamide （PZA）, amikacin （AMK）, levofloxacin （LVFX）, multidrug-resistant （MDR）, pan-drug Resistance （XDR） in SIT1 genotype were higher than Above SIT53, SIT52, SIT19. But resistance of SIT523 in RFP, SM, EMB, MDR were higher than SIT1. （3）The resistance of of INH, PZA and AMK in the Beijing family was higher than the non-Beijing family. The difference was statistically significant （P〈0.05）. There was no significant difference inother drugs （P〉 0.05）.MTB in Guangdong was genetically polymorphic, and the Beijing genotype strain was the main epidemic strain of MTB in the province, and was associated with resistance to isoniazid, pyrazinamide, and amikacin. Non-Beijing genotypes have increased in the proportion of overseas Chinese living in Chaoshan and Dongguan.