长沙某医院结核分枝杆菌耐药基因分布情况分析
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摘要
目的了解长沙某医院结核分枝杆菌(MTB)耐药基因的分布情况。方法分析长沙市中心医院2014年7月至2017年3月分离的1 981株MTB耐药基因ropB、KatG和inhA的分布情况。结果 1 981例MTB感染患者中共检出ropB基因突变型335株,突变率为16.91%(335/1 981)。ropB基因位点突变率由高至低依次为531[50.75%(170/335)]、516[21.19%(71/335)]、526[17.0%(157/335)]、511[14.33%(48/335)]、513[2.69%(9/335)]、533[2.39%(8/335)];检出KatG突变株310株,突变率为15.65%(310/1 981);inhA突变型68株,突变率为3.43%(68/1 981),合计耐异烟肼基因突变率为18.6%(369/1 981)。其中KatG AGC→ACC突变型占79.95%(295/369)。结论 ropB基因531、516、526和511位点突变和KatG AGC→ACC突变是导致长沙某院结核病利福平和异烟肼耐药的主要因素,基因芯片技术可作为该院MTB耐药基因的快速筛选方法。
Objective To study the distribution of MTB resistance genes in Changsha Central Hospital.Methods Totally 1981 strains of MTB were identified in Changsha Central Hospital from July 2014 to March2017,resistant genes ropB 、KatG and inhA were screened by DNA microarray.Results A total of 335 ropB mutant strains were detected,with a mutation rate of 16.91%(335/1981).Site mutation rates were followed by 531(171/335,50.75%),516(71/335,21.19%),526(57/335,17.01),511(48/335,14.33%),513(9/335,2.69%),and 533(8/335,2.39%);The KatG mutant was detected in 310 strains,the mutation rate was15.65%(310/1981);the inhA mutant was 68,and the mutation rate was 3.43%(68/1981).The total mutation rate of isoniazid resistant genes was 18.6%(369/1981).KatG AGC→ACC mutant accounted for 79.95%(295/369).Conclusion Mutations of the 531,516,526 and 511 loci of ropB gene and mutations of KatG AGC→ACC are the main factors resulting RFP and isoniazid resistance in tuberculosis in Changsha Central Hospital.DNA microarray can be used as a rapid screening method for MTB resistance genes in Changsha.
Objective To study the distribution of MTB resistance genes in Changsha Central Hospital.Methods Totally 1981 strains of MTB were identified in Changsha Central Hospital from July 2014 to March2017,resistant genes ropB 、KatG and inhA were screened by DNA microarray.Results A total of 335 ropB mutant strains were detected,with a mutation rate of 16.91%(335/1981).Site mutation rates were followed by 531(171/335,50.75%),516(71/335,21.19%),526(57/335,17.01),511(48/335,14.33%),513(9/335,2.69%),and 533(8/335,2.39%);The KatG mutant was detected in 310 strains,the mutation rate was15.65%(310/1981);the inhA mutant was 68,and the mutation rate was 3.43%(68/1981).The total mutation rate of isoniazid resistant genes was 18.6%(369/1981).KatG AGC→ACC mutant accounted for 79.95%(295/369).Conclusion Mutations of the 531,516,526 and 511 loci of ropB gene and mutations of KatG AGC→ACC are the main factors resulting RFP and isoniazid resistance in tuberculosis in Changsha Central Hospital.DNA microarray can be used as a rapid screening method for MTB resistance genes in Changsha.
引文
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[7]王峰,桂静,赵广录,等.基因芯片检测结核分枝杆菌利福平异烟肼耐药性的应用评价[J].中华检验医学杂志,2012,35(12):1125-1129.
[8]潘建华,罗丹,石国民,等.2012-2015年长沙地区肺结核患者结核分枝杆菌耐药状况分析[J].现代预防医学,2016,43(8):1499-1501.
[9]欧维正,骆科文,陈峥宏,等.贵州地区结核分枝杆菌利福平耐药相关基因rpoB突变特征分析[J].中国临床药理学杂志,2015,31(10):833-835.
[10]欧维正,陈峥宏,陈静,等.基因芯片技术检测贵州省结核分枝杆菌耐药基因KatG和inhA[J].中国人兽共患病学报,2015,31(7):655-658.
[11]桂静,王峰.深圳地区结核分枝杆菌耐药分离株分子特征与表型特征相关性研究[J].中华微生物学和免疫学杂志,2010,30(5):466-471.
[12]许榕青,李丹,林银霞,等.基因芯片技术检测结核分枝杆菌利福平和异烟肼耐药性临床应用评价[J].中国人兽共患病学报,2017,33(1):43-48.
[13]戎奇吉,吕火祥,孙爱华.基因芯片快速检测结核分枝杆菌KatG基因突变及其与异烟肼耐药相关性[J].中国人兽共患病学报,2011,27(3):233-237.
[14]马峻,陈高瞻,董洁莉,等.武汉地区耐异烟肼结核分枝杆菌临床分离株KatG基因突变的分子特征分析[J].中国防痨杂志,2014,37(1):95-97.
[2] PANG Y,XIA H,ZHANG Z,et al.Multicenter evaluation of genechip for detection of multidrug-resistant Mycobacterium tuberculosis[J].J Clin Microbiol,2013,51(6):1707-1713.
[3]邓叶华,向延根,马小华,等.基因芯片法用于检测长沙地区结核分枝杆菌耐药性研究[J].国际检验医学杂志,2015,36(22):3223-3226.
[4] KHOSRAVI A D,GOODARZI H,ALAVI S M.Detection of genomic mutations in katG,inhA and rpoB genes of Mycobacterium tuberculosis isolates using polymerase chain reaction and multiplex allele-specific polymerase chain reaction[J].Braz J Infect Dis,2012,16(1):57-62.
[5] HEYSELL S K,HOUPT E R.The future of molecular diagnostics for drug-resistant tuberculosis[J].Expert Rev Mol Diagn,2012,12(4):395-405.
[6]李同霞,江国峰,郝文嘉,等.结核分枝杆菌临床分离株利福平和异烟肼耐药性检测方法比较[J].中国现代医学杂志,2016,26(24):24-27.
[7]王峰,桂静,赵广录,等.基因芯片检测结核分枝杆菌利福平异烟肼耐药性的应用评价[J].中华检验医学杂志,2012,35(12):1125-1129.
[8]潘建华,罗丹,石国民,等.2012-2015年长沙地区肺结核患者结核分枝杆菌耐药状况分析[J].现代预防医学,2016,43(8):1499-1501.
[9]欧维正,骆科文,陈峥宏,等.贵州地区结核分枝杆菌利福平耐药相关基因rpoB突变特征分析[J].中国临床药理学杂志,2015,31(10):833-835.
[10]欧维正,陈峥宏,陈静,等.基因芯片技术检测贵州省结核分枝杆菌耐药基因KatG和inhA[J].中国人兽共患病学报,2015,31(7):655-658.
[11]桂静,王峰.深圳地区结核分枝杆菌耐药分离株分子特征与表型特征相关性研究[J].中华微生物学和免疫学杂志,2010,30(5):466-471.
[12]许榕青,李丹,林银霞,等.基因芯片技术检测结核分枝杆菌利福平和异烟肼耐药性临床应用评价[J].中国人兽共患病学报,2017,33(1):43-48.
[13]戎奇吉,吕火祥,孙爱华.基因芯片快速检测结核分枝杆菌KatG基因突变及其与异烟肼耐药相关性[J].中国人兽共患病学报,2011,27(3):233-237.
[14]马峻,陈高瞻,董洁莉,等.武汉地区耐异烟肼结核分枝杆菌临床分离株KatG基因突变的分子特征分析[J].中国防痨杂志,2014,37(1):95-97.