汉族儿童Ⅱ相药物代谢酶基因GSTM1和GSTT1的多态性分布  

Polymorphisms distribution of phase Ⅱ drug metabolic enzyme gene GSTM1 and GSTT1 in Chinese Han pediatric population

作　　者：刘芳[1] 苗青[1] 肖婧[1] 孙琳[1] 申晨[1] 焦伟伟[1] 冯卫星[1] 吴喜蓉[1] 申丹[1] 申阿东[1] 

机构地区：[1]首都医科大学附属北京儿童医院,北京市儿科研究所,儿科学国家重点学科,省部共建儿科重大疾病研究重点实验室,北京100045

出　　处：《中国循证儿科杂志》2011年第3期205-210,共6页Chinese Journal of Evidence Based Pediatrics

基　　金：国家自然科学基金面上项目:30872788,81071315

摘　　要：目的了解谷胱甘肽-S-转移酶M1(GSTM1)和T1(GSTT1)基因多态性在中国汉族儿童中的分布特点,为临床针对不同基因型个体化药物治疗提供理论基础。方法选择首都医科大学附属北京儿童医院健康查体汉族儿童的血样,提取DNA。应用PCR法检测GSTM1和GSTT1基因型,并判断代谢表型。检索PubM ed等数据库,获得亚洲人群、黑种人和高加索人群GSTM1和GSTT1基因多态性分布的数据,与本研究分析人群数据进行比较,分析基因多态性的种族差异。结果 786份研究样本纳入分析。①中国汉族分析人群GSTM1和GSTT1完全缺失基因型/慢代谢型(*0/*0)的频率分别为59.3%(466/786例)和58.4%(459/786例);单拷贝缺失基因型/中间代谢型(*1/*0)的频率分别为34.0%(267/786例)和35.1%(276/786例);未缺失基因型/快代谢型(*1/*1)的频率分别为6.7%(53/786例)和6.5%(51/786例)。②GSTM1和GSTT1基因多态性分布互相独立,无明显关联。③GSTM1和GSTT1基因多态性无显著性别差异。④本研究汉族分析人群GSTM1和GSTT1基因多态性分布与亚洲人群较为接近,与黑种人和高加索人群有显著差异。结论 GSTM1和GSTT1基因在中国汉族儿童中以完全缺失基因型/慢代谢型(*0/*0)为主,具有种族特异性,为不同基因型个体制定合适的用药方案提供了参考依据。Objective Human glutathione S-transferases（hGSTs） play a crucial role in the biological detoxification processes of drugs and xenobiotics.In drug metabolic process,the gene polymorphism caused by a homozygous or heterozygous deletion of the GSTM1 and GSTT1 genes was associated with the metabolic speed of glutathione S-transferases.The aim of this study was to investigate the association between gene polymorphisms and the metabolic phenotype of GSTM1 and GSTT1 in normal Chinese Han children,to provide an important theoretical basis for guiding the clinical treatment of drugs which metabolic by liver.Methods Chinese Han healthy children were identified who were randomly sampled from 2005 to 2010 in healthy center of Beijing Children＇s Hospital.The mean age of them was 5.425 years,ranged from 2 months to 14 years.The participants with positive history of diagnosed cancers,psychiatric disorders,asthma,cataract and cardiovascular disease showing significant association with hGSTs polymorphism were excluded.Demographic and medical information of these children was obtained from the patients＇ files.Genomic DNA was extracted from peripheral blood by EDTA anticoagulation,using a standard salting-out procedure.The concentration and purity of DNA were estimated spectrophotometrically.Genotyping was carried out by using traditional PCR-RFLP method.Further comparison between our existing data and previously reported frequencies in other ethnic populations,was performed to determine inter-ethnic differences.Results A total of 786 Chinese Han healthy children（486 males and 300 females） were enrolled into the study.In the study population,homozygous deletion（＊0/＊0） referring to slow metabolism was detected in 59.3%（n=466） for GSTM1 gene and 58.4%（n=459）for GSTT1 gene of the subjects,GSTM1 and GSTT1 homozygous deletions（＊0/＊0） respectively.The heterozygous deletion（＊1/＊0） referring to middle metabolism was detected in 34.0%（n=267） for GSTM1 gene and 35.1%（n=276） for GSTT1 gene o

关 键 词：谷胱甘肽-S-转移酶M1 谷胱甘肽-S-转移酶T1 基因多态性 药物代谢 中国汉族儿童 个体化用药 

分 类 号：R96[医药卫生—药理学]