上海地区汉族人谷胱甘肽S转移酶基因多态性分析(英文)

Glutathione S Transferase Polymorphism in Han Nationality in Shanghai

摘要:

目的：测定GST基因在上海地区健康汉族人中的遗传多态性，筛选出汉族人的GST候选单核苷酸多态性(SNP)位点，为开展GST基因多态性与汉族人群肿瘤易感性及治疗相关性研究作一初步探索。方法：采用荧光标记自动测序法，筛选GSTT1，GSTM1基因在20名上海地区的汉族健康志愿者中的候选SNP位点。结果：4例受检者在GSTT1外显子4和3之间的第86 057位点发生点突变，由腺嘌呤A取代鸟嘌呤G，经与Genebank中SNP数据库比对，可能为一新的GSTT1基因候选SNP位点；在外显子5的第793位点和921位点，所有受检者均为G&A的杂合子。GSTM1在8个外显子中均发现有候选SNP位点，但多为单核苷酸的杂合子。约40%受检者的外显子2出现腺嘌呤A缺失，所有受检者在第1 383位点和1 385位点分别是A&G受C&G杂合子；在第101位点60%个体为A&T杂合，40%个体为腺嘌呤A的纯合子。我们还初步发现在外显子2的190 bp以后可能存在多个碱基或小片段缺失。结论：上海地区健康汉族人的GST基因具有丰富的遗传多态性。这些多态性是否为汉族人所特有、与肿瘤易感性的关系，以及这些可能的候选SNP位点是否会造成其编码氨基酸的改变并引起产物蛋白一级结构的变化、进而导致GST酶活性发生改变而表现为具有不同的表型及基因型，尚需深入探讨。

Abstract:

OBJECTIVE: In order to develop a primary exploration of the relationship between glutathione S transferase (GST) polymorphism and tumor susceptibility or therapeutic correlation in Han nationality, the genetic polymorphism of GST in healthy Han nationality of Shanghai was investigated and the candidate's single nucleotide polymorphism (SNP) was screened. METHODS: Automatic sequencing with labelled fluorescence was used to screen the SNPs of GSTT1 and GSTM1 in 20 healthy Han people. RESULTS: Point mutation was found at 86 057 site between exon 4 and exon 3 of GSTT1 in 4 cases, with guanine G substituted by adenine A. It may be a new candidate's SNP of GSTT1 after compared with genebank's SNP database. G&A heterozygotes could be found at 793 site and 921 site of exon 5 in all cases. Many candidate's SNPs were discovered in all 8 exons of GSTM1 and most of them were heterozygotes. 40% of the examinees showed adenine A deletion in exon 2. All examinees were A&G heterozygotes at 1 383 site and C&G heterozygotes at 1 385 site. At 101 site, 60% of the people examined showed A&T heterozygotes and 40% of the people had adenine A homozygotes. We found deletion of many base pairs or short fragments after 190 bp of exon 2. CONCLUSIONS: The genetic polymorphism of GST varies greatly in healthy Han people in Shanghai. It remains to be discussed further whether the polymorphisms only occurred in Han nationals and correlated with tumor susceptibility and whether these possible candidate's SNPs could alter amino acid code resulting in variation of the primary structure of protein and alteration of GST acitivity.