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

  更多相關文章： 結核分枝桿菌 分子流行病學 基因分型 間隔區(qū)寡核苷酸分型(Spolgotyping) 散在分布重復單位-數目可變串聯(lián)重復序列(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,比較465株分枝桿菌間隔區(qū)寡核苷酸分型(Spoligotyping)和散在分布重復單位-數目可變串聯(lián)重復序列(MIRU-VNTR)兩種基因型方法試驗結果的異同,分析北京基因型與耐藥性的相互關系,從而探討北京地區(qū)結核分枝桿菌的分子流行特點,分析結核分枝桿菌的耐藥性特點及其同分子流行病學的聯(lián)系,并評價兩種基因分型方法。方法對收集的北京市679株分枝桿菌臨床分離株進行Spoligotyping基因分型研究,其中的465株分枝桿菌同時運用MIRU-VNTR方法進行基因分型研究。用NatureEdge軟件和BioNumerics軟件將分型結果進行聚類分析。應用比例法藥物敏感試驗對268株結核分枝桿菌進行檢測,最后將藥敏結果結合流行病學資料進行分析。采用χ2檢驗比較不同組間結果的差別。結果在分離培養(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。未接種過卡介苗(BCG)的患者中北京基因型菌株占83.5%(240/269),接種過BCG的患者中北京基因型菌株占81.7%(384/470),兩者差異無統(tǒng)計學意義。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),但二者差異也無統(tǒng)計學意義。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個基因型。本地戶籍成為菌株成簇的一個危險因素,OR值為1.90。VNTR方法對465株分枝桿菌的分辨率指數為0.9576。對北京基因型的分辨率指數為0.9547,同樣顯示了很高的分辨率指數。而Spoligotyping分型方法對465株分枝桿菌的分辨率指數0.4131,對北京基因型的分辨率指數為0.1430,低于MIRU-VNTR方法。不同的菌株和同一菌株在不同位點的MIRU-VNTR DNA指紋圖譜呈現出多態(tài)性,各位點呈現的等位基因多態(tài)性有差異,多態(tài)性最高的位點是QUB-11b,多態(tài)性最低的位點為QUB-4156c。對北京基因型位點多態(tài)性分析也顯示了相同的最高位點和最低位點。結論北京基因型菌株2008年在北京地區(qū)有廣泛分布,為占絕對優(yōu)勢的菌株；北京基因型菌株與BCG接種無關,與一線、二線抗結核藥物耐藥無關；結核病患者中有部分是由于近期傳播而引起的。MIRU-VNTR基因分型方法能夠對Spoligotyping分型結果繼續(xù)分型,分辨率指數要高于Spoligotyping分型方法。MIRU-VNTR分型方法對所有基因型和對北京基因型的分辨指數差別不大。Spoligotyping分型方法對北京基因型的分辨率指數較低。
[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.
【學位授予單位】：北京市結核病胸部腫瘤研究所
【學位級別】：博士
【學位授予年份】：2012
【分類號】：R378.911

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本文編號：1341477