糖尿病对结核分枝杆菌rpoB基因耐药位点突变影响的相关性  

Correlation of diabetes with mutation of rpoB gene resistance site of Mycobacterium tuberculosis

作　　者：吴海丰 刘瑞 王洁莹 李小丽 吴秋萍 俞亚转 李文庭 WU Haifeng;LIU Rui;WANG Jieying;LI Xiaoli;WU Qiuping;YU Yazhuan;LI Wenting(The Second Affiliated Hospital of Hainan Medical University,Haikou,Hainan 570311,China)

机构地区：[1]海南医学院第二附属医院,海南海口570311

出　　处：《中国热带医学》2024年第9期1094-1099,共6页China Tropical Medicine

基　　金：2022年度(第一批)海南省卫生健康行业科研项目(No.22A200076);海南省临床医学中心建设项目(No.琼卫涵2021-276)。

摘　　要：目的了解耐药肺结核合并糖尿病患者利福平rpoB基因突变位点的分子特征,探讨合并糖尿病是否影响利福平耐药相关基因突变,为肺结核合并糖尿病共病的防治提供数据支持。方法选取2022—2023年在海南医学院第二附属医院就诊经痰液或肺泡灌洗液分枝杆菌培养和药敏试验确诊为利福平耐药肺结核患者170例。根据是否合并糖尿病分为单纯耐利福平肺结核组(RR-TB)102例和耐利福平肺结核合并糖尿病组(RR-TB+DM)68例。采用微阵列芯片法对所有患者的痰液或肺泡灌洗液样本进行利福平rpoB基因位点检测,分析两组患者的利福平耐药基因位点突变特征和差异。结果男性、复治、涂阳、40~<60岁年龄段人群发生利福平耐药比例较高,但两组差异均无统计学意义(P>0.05);20~<40岁年龄段患者在RR-TB+DM组的比例(11.8%,8/68)显著低于RR-TB组(24.5%,25/102)(χ^(2)=4.237,P<0.05);两组患者rpoB基因突变位点均以531、526和511位点为主,但位点突变频率的排序略有不同。RR-TB+DM组最常见的突变位点依次为531(57.4%,39/68)、526(19.1%,13/68)和511(8.9%,6/68),而RR-TB组则为531(51.9%,53/102)、526(18.6%,19/102)和511(14.8%,15/102),但两组间差异无统计学意义(P>0.05);531突变主要以TCG→TTG为主,526主要有4种突变类型,其中CAC→TAC为主要突变类型,RR-TB组526主要突变型为CAC→GAC,而在RRTB+DM组中526位点无CAC→GAC突变,两组比较差异有统计学意义(P<0.05),511主要以CTG→CCG突变为主,但两组比较无显著性差异(P>0.05)。结论合并糖尿病肺结核rpoB526CAC→GAC突变率及20~<40岁利福平耐药占比明显低于单纯肺结核,提示糖尿病可能影响该位点的基因突变。Objective To understand the molecular characteristics of rifampicin rpoB gene mutation site in patients with rifampin-resistant pulmonary tuberculosis(RR-TB)complicated with diabetes mellitus,and to explore whether the combination of diabetes mellitus affects rifampicin resistance-related gene mutation,providing data support for prevention and treatment of tuberculosis complicated with diabetes comorbidity.Methods A total of 170 patients with rifampicin-resistant pulmonary tuberculosis diagnosed by mycobacterium culture in sputum or alveolar lavage fluid and drug sensitivity test at the Second Affiliated Hospital of Hainan Medical University from 2022 to 2023 were selected.According to whether they were comorbid with diabetes,patients were divided into two groups:rifampicin-resistant tuberculosis without diabetes group(RRTB;n=102)and rifampicin-resistant tuberculosis with diabetes group(RR-TB+DM;n=68).Rifampicin rpoB gene loci were detected in sputum or alveolar lavage fluid samples from all patients by microarray method,and the mutation characteristics of rifampicin resistance loci in the two groups were analyzed to explore the differences of drug resistance loci.Results The proportion of rifampicin resistance was higher in males,retreatment,smear positive and 40 to<60years old,but there was no statistically significant difference between the two groups(P>0.05);the proportion of patients aged 20 to<40 years in RR-TB+DM group(11.8%,8/68)was significantly lower than that in the RR-TB+DM group(24.5%,25/102)(χ^(2)=4.237,P<0.05);the main mutation sites of the rpoB gene in both groups were 531,526 and 511,but the mutation frequency of the sites was slightly different.The most common mutation sites in RR-TB+DM group were 531(57.4%,39/68),526(19.1%,13/68),and 511(8.9%,6/68),whereas in the RR-TB group,they were 531(51.9%,53/102),526(18.6%,19/102),and 511(14.8%,15/102),but there was no significant difference between the two groups(P>0.05).The mutation of 531 was mainly TCG→TTG.The 526 had four mutation types,with CAC�

关 键 词：耐药肺结核 糖尿病 利福平 RPOB基因 突变位点 

分 类 号：R521.1[医药卫生—内科学]