本文關(guān)鍵詞：北京地區(qū)結(jié)核分枝桿菌基因分型及與耐藥性關(guān)系的研究　出處：《北京市結(jié)核病胸部腫瘤研究所》2012年博士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 結(jié)核分枝桿菌 分子流行病學(xué) 基因分型 間隔區(qū)寡核苷酸分型(Spolgotyping) 散在分布重復(fù)單位-數(shù)目可變串聯(lián)重復(fù)序列(MIRU-VNTR)

【摘要】：目的了解北京地區(qū)679株分枝桿菌臨床分離株的基因型分布、主要流行特點(diǎn),比較465株分枝桿菌間隔區(qū)寡核苷酸分型(Spoligotyping)和散在分布重復(fù)單位-數(shù)目可變串聯(lián)重復(fù)序列(MIRU-VNTR)兩種基因型方法試驗(yàn)結(jié)果的異同,分析北京基因型與耐藥性的相互關(guān)系,從而探討北京地區(qū)結(jié)核分枝桿菌的分子流行特點(diǎn),分析結(jié)核分枝桿菌的耐藥性特點(diǎn)及其同分子流行病學(xué)的聯(lián)系,并評(píng)價(jià)兩種基因分型方法。方法對(duì)收集的北京市679株分枝桿菌臨床分離株進(jìn)行Spoligotyping基因分型研究,其中的465株分枝桿菌同時(shí)運(yùn)用MIRU-VNTR方法進(jìn)行基因分型研究。用NatureEdge軟件和BioNumerics軟件將分型結(jié)果進(jìn)行聚類分析。應(yīng)用比例法藥物敏感試驗(yàn)對(duì)268株結(jié)核分枝桿菌進(jìn)行檢測(cè),最后將藥敏結(jié)果結(jié)合流行病學(xué)資料進(jìn)行分析。采用χ2檢驗(yàn)比較不同組間結(jié)果的差別。結(jié)果在分離培養(yǎng)的679株菌株中,具有特異Spoligotyping指紋圖譜的北京基因型菌株在北京地區(qū)分布達(dá)82.6%(561/679),為北京地區(qū)2008年主要流行的基因型菌株。未接種過(guò)卡介苗(BCG)的患者中北京基因型菌株占83.5%(240/269),接種過(guò)BCG的患者中北京基因型菌株占81.7%(384/470),兩者差異無(wú)統(tǒng)計(jì)學(xué)意義。十種藥物耐藥性由高到低依次為丁胺卡那霉素(61.76%)、利福平(54.65%)、乙硫異煙胺(44.16%)、利福布汀(39.71%)、異煙肼(23.37%)、鏈霉素(22.22%)、左氧氟沙星(18.87%)、對(duì)氨基水楊酸(8.70%)、卷曲霉素(6.52%)、乙胺丁醇(4.71%)。北京基因型菌株耐藥率為86.11%(186/216),低于非北京基因型菌株的耐藥率93.18%(41/44),但二者差異也無(wú)統(tǒng)計(jì)學(xué)意義。Spoligotyping分型方法顯示成簇菌株占所有菌株的93.93%(437/465),分73個(gè)基因型,MIRU-VNTR分型方法顯示成簇菌株占所有菌株的22.37%(104/465),398個(gè)基因型。本地戶籍成為菌株成簇的一個(gè)危險(xiǎn)因素,OR值為1.90。VNTR方法對(duì)465株分枝桿菌的分辨率指數(shù)為0.9576。對(duì)北京基因型的分辨率指數(shù)為0.9547,同樣顯示了很高的分辨率指數(shù)。而Spoligotyping分型方法對(duì)465株分枝桿菌的分辨率指數(shù)0.4131,對(duì)北京基因型的分辨率指數(shù)為0.1430,低于MIRU-VNTR方法。不同的菌株和同一菌株在不同位點(diǎn)的MIRU-VNTR DNA指紋圖譜呈現(xiàn)出多態(tài)性,各位點(diǎn)呈現(xiàn)的等位基因多態(tài)性有差異,多態(tài)性最高的位點(diǎn)是QUB-11b,多態(tài)性最低的位點(diǎn)為QUB-4156c。對(duì)北京基因型位點(diǎn)多態(tài)性分析也顯示了相同的最高位點(diǎn)和最低位點(diǎn)。結(jié)論北京基因型菌株2008年在北京地區(qū)有廣泛分布,為占絕對(duì)優(yōu)勢(shì)的菌株；北京基因型菌株與BCG接種無(wú)關(guān),與一線、二線抗結(jié)核藥物耐藥無(wú)關(guān)；結(jié)核病患者中有部分是由于近期傳播而引起的。MIRU-VNTR基因分型方法能夠?qū)poligotyping分型結(jié)果繼續(xù)分型,分辨率指數(shù)要高于Spoligotyping分型方法。MIRU-VNTR分型方法對(duì)所有基因型和對(duì)北京基因型的分辨指數(shù)差別不大。Spoligotyping分型方法對(duì)北京基因型的分辨率指數(shù)較低。
[Abstract]:Objective to understand the Beijing region of 679 strains of genotype of Mycobacterium tuberculosis strains distribution, epidemic characteristics, 465 strains of Mycobacterium type spacer oligonucleotide (Spoligotyping) and scattered distribution of variable number of tandem repeat repeat units (MIRU-VNTR) between the two genotypes of test results, analysis of the relationship between Beijing genotype with the resistance, so as to explore the molecular epidemiological characteristics of Mycobacterium tuberculosis in Beijing area, with the analysis of resistance characteristics and molecular epidemiology of Mycobacterium tuberculosis contact, and evaluate the two genotyping methods. Methods a total of 679 Mycobacterium clinical isolates from Beijing were analyzed for Spoligotyping genotyping. 465 Mycobacterium strains were genotyping by MIRU-VNTR. NatureEdge software and BioNumerics software were used to cluster analysis. 268 strains of Mycobacterium tuberculosis were detected by using the proportion method of drug sensitivity test. Finally, the results of drug sensitivity were analyzed with epidemiological data. The difference between the results of different groups was compared with the x 2 test. Results among the 679 strains isolated and cultured, the Beijing genotype Spoligotyping with specific 561/679 fingerprints distributed 82.6% (561/679) in Beijing area, which was the most popular genotype in Beijing area. Among the patients who had not been vaccinated with Bacillus Calmette Guerin vaccine (BCG), the genotype of Beijing accounted for 83.5% (240/269), while the genotype of Beijing genotype accounted for 81.7% (384/470), and the difference between the two was not statistically significant (BCG). Ten kinds of drug resistance from high to low were amikacin (61.76%), Li Fuping (54.65%), ethionamide (44.16%), Leigh Fob Dean (39.71%), (23.37%) isoniazid and streptomycin (22.22%), levofloxacin (18.87%), salicylic acid (8.70%), capreomycin (6.52%), ethambutol (4.71%). The resistance rate of Beijing genotype was 86.11% (186/216), and the resistance rate of the non Beijing genotype was 93.18% (41/44), but the difference between the two strains was not statistically significant. The Spoligotyping typing method showed that the cluster strains accounted for 93.93% (437/465) of all strains, which were divided into 73 genotypes. The MIRU-VNTR typing method showed that the cluster strains accounted for 22.37% (104/465) and 398 genotypes of all strains. Local domicile has become a risk factor for the cluster of strains, with a OR value of 1.90. The resolution index of the VNTR method for 465 Mycobacterium strains was 0.9576. The resolution index of the Beijing genotypes was 0.9547, which also showed a high resolution index. The resolution index of Spoligotyping typing for 465 strains of Mycobacterium was 0.4131, and the resolution index of Beijing genotypes was 0.1430, which was lower than that of MIRU-VNTR. The MIRU-VNTR DNA fingerprints of different strains and the same strain at different loci showed polymorphism. The alleles polymorphism at each loci was different. The most polymorphic locus was QUB-11b, and the lowest polymorphism locus was QUB-4156c. The polymorphism analysis of the genotypic loci in Beijing also showed the same highest site and the lowest point. Conclusion Beijing genotype strains were widely distributed in Beijing area in 2008. They are the most dominant strains. The genotype of Beijing has nothing to do with BCG vaccination. It is not related to the resistance of first-line and second-line anti tuberculosis drugs. Some of the tuberculosis patients are caused by recent transmission. The MIRU-VNTR genotyping method can continue to be typed for the results of Spoligotyping typing, and the resolution index is higher than that of the Spoligotyping typing. MIRU-VNTR typing has little difference in the resolution index of all genotypes and Beijing genotypes. The resolution index of the genotyping of the Beijing genotypes was lower than that of the Beijing genotyping.
【學(xué)位授予單位】：北京市結(jié)核病胸部腫瘤研究所
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2012
【分類號(hào)】：R378.911

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