中国人群N-乙酰基转移酶2基因型分布特征及不同基因分型方法的比较  

Distribution characteristics of N-acetyltransferase-2 genotypes and comparison methods of different genotyping in Chinese population

作　　者：王宁 郑璐瑶 孟秀娟[2] 刘海婷 丁杨明 姚蓉 郭少晨[1] 陆宇[1] WANG Ning;ZHENG Lu-yao;MENG Xiu-juan;LIU Hai-ting;DING Yang-ming;YAO Rong;GUO Shao-chen;LU Yu(Beijing Key Laboratory of Drug Resistance Tuberculosis Research,Beijing Tuberculosis and Thoracic Tumor Research Institute/Beijing Chest Hospital,Capital Medical University,Beijing 101149,China;Department of Hospital Infection Control Center,Xiangya Hospital Central South University,Changsha 410008,China)

机构地区：[1]北京市结核病胸部肿瘤研究所/首都医科大学附属北京胸科医院药物研究室,北京101149 [2]中南大学湘雅医院医院感染控制中心,长沙410008

出　　处：《中国防痨杂志》2022年第6期625-634,共10页Chinese Journal of Antituberculosis

基　　金：首都临床诊疗技术研究及示范应用项目(Z191100006619090);北京市医院管理中心临床医学发展专项(ZYLX202123)。

摘　　要：目的:分析中国人群N-乙酰基转移酶2(N-acetyltransferase-2,NAT2)基因型分布特征及不同基因分型方法的效能。方法:对包含中国人群NAT2基因多态性数据的文献进行检索,检索范围包括Medline、PubMed、Embase、维普中文科技期刊数据库、中国知网和万方医学网等数据库,检索时限为数据库建库至2021年12月1日。英文检索词:NAT2、N-acetyltransferase、polymorphism、China或Chinese等;中文检索词:NAT2、基因多态性、中国等。使用Newcastle-Ottawa Scale(NOS)评分表对纳入的文献进行质量评价和风险评估。提取文献中NAT2基因型及等位基因信息,重建单项研究NAT2基因型数据库并利用Phase 2.1软件进行单体型和双体型重建及验证。构建中国人群NAT2基因型分布数据库,分析NAT2等位基因和基因型分布特点。基于构建的NAT2基因型数据库,评估不同NAT2基因型分型推断方法的效能。结果:经过文献检索及筛选,共有10项研究的结果纳入本研究。汇总纳入10项研究中对照组4010例个体的基因型数据,NAT2快代谢基因型、中间代谢基因型、慢代谢基因型总体频率分别为25.79%(1034/4010)、50.87%(2040/4010)、23.34%(936/4010),NAT2非慢代谢基因型总体频率为76.66%(3074/4010);NAT2快、慢代谢等位基因总体携带频率分别为51.19%(4096/8002)及48.81%(3906/8002)。3SNP法推断NAT2慢代谢基因型的敏感度和特异度分别为99.92%(1249/1250)和99.81%(4190/4198);推断NAT2快代谢基因型的敏感度和特异度分别为100.00%(1484/1484)和99.92%(3961/3964)。2SNP法推断NAT2慢代谢基因型的敏感度和特异度分别为99.52%(1194/1250)和98.36%(4129/4198);推断NAT2快代谢基因型的敏感度和特异度分别为93.19%(1383/1484)和96.01%(3806/3964)。3SNP法和2SNP法推断NAT2慢代谢基因型敏感度差异无统计学意义(χ^(2)=0.189,P=0.664),一致性较好(Kappa=0.932)。3SNP法推断NAT2快代谢基因型敏感度优于2SNP法(χ^(2)=10.973,P=0.001)。结论:�Objective:To analyze the distribution characteristics of N-acetyltransferase-2(NAT2)genotypes and the effectiveness of different genotyping methods in Chinese population.Methods:The literatures containing NAT2 gene polymorphism data of Chinese population were retrieved in Medline,PubMed,Embase,China Science and Technology Journal Database,China National Knowledge Internet,and Wanfang database.The retrieval time limit was from the establishment of the database to December 1,2021,with the English search words of NAT2,N-acetyltransferase,polymorphism,China or Chinese,etc.,and Chinese search words of NAT2,gene polymorphism,China,etc..Newcastle Ottawa scale(NOS)was used to evaluate the quality and bias risk of the included literature.The NAT2 genotype and allele data in the literature were extracted,the NAT2 genotype database of single study was reconstructed,and the haplotype and diplotype were reconstructed and verified by phase 2.1 software.The NAT2 genotype of the control group in the literature were extracted to construct the NAT2 genotype distribution database of Chinese population,and the distribution characteristics of NAT2 alleles and genotypes were analyzed.Based on the constructed NAT2 genotype database,the efficiency of different NAT2 genotyping panels was evaluated.Results:Through literature retrieval and screening,the results of 10 studies were included.The genotype data in the control group of 4010 individuals were summarized.The overall frequencies of NAT2 fast,intermediate and slow metabolism genotype were 25.79%(1034/4010),50.87%(2040/4010)and 23.34%(936/4010),respectively,the total frequency of NAT2 non-slow metabolism genotype was 76.66%(3074/4010);the total frequencies of NAT2 fast and slow metabolism alleles were 51.19%(4096/8002)and 48.81%(3906/8002),respectively.Using 3SNP method,the sensitivity and specificity of NAT2 slow metabolism genotype inferring were 99.92%(1249/1250)and 99.81%(4190/4198),and were 100.00%(1484/1484)and 99.92%(3961/3964)in NAT2 fast metabolism genotype inferring.Using 2S

关 键 词：乙酰基转移酶类 基因型 等位基因 人群监测 中国 

分 类 号：R968[医药卫生—药理学]