【摘要】 背景与目的:研究发现谷胱甘肽硫转移酶M1(glutathione S-tranferase M1,GSTM1)基因缺失可使患鼻咽癌的危险性增加。本研究旨在通过对GSTM1基因编码区单核苷酸多态(single nucleotide polymorphism,SNP)位点的研究,来评估其与中国南方人群鼻咽癌遗传易感性的关系。方法:239例鼻咽癌患者和286例健康人群入组该实验。其中225例鼻咽癌患者及273例对照的实验结果用于统计学分析。在GSTM1基因外显子区、内含子和外显子交界区设计引物,用PCR产物直接测序(测序总长度4739bp),从中获得SNP位点。选择编码区多态位点T1270533G和C1256088C,用tetra-PrimerARMS-PCR和测序方法进行病例-对照研究。结果:通过测序共获取29个SNPs编码区。T1270533G和C1256088C位点氨基酸的密码子分别发生了碱基顛换,产生了错义突变。对225例鼻咽癌患者和273例健康人群分型结果表明T1270533G位点的变异与鼻咽癌临床表型之间无明显关联(OR=0.170,纯合子TT95%CI=0.95-0.306)。C1256088C位点缺失率在鼻咽癌人群中为45%(45/100),在对照人群中为42%(42/100)。结论:编码区T1270533G位点的多态性并没有影响该基因的解毒功能。该位点与中国南方人群鼻咽癌遗传易感性无明显关联。本组多态性位点C1256088C缺失率高。更多还原

【Abstract】 Background and Objective: Glutathione S-transferase M1 (GSTM1) deficiency may increase the risk of nasopharyngeal carcinoma (NPC). This study was to evaluate the correlation of the single nucleotide polymorphism (SNP) in the coding region of GSTM1 gene to NPC susceptibility in southern China population. Methods: In total 239 NPC patients and 286 age-matched healthy controls were entered into the study. Among them, 225 out of 239 NPC patients and 273 out of 286 controls were used for statistical analysis. SNP screening of all exons, relevant intron-exon boundaries, and the promoter region of GSTM1, in total 4739bp, was performed by PCR direct sequencing. The loci T1270533G and C1256088C were selected for the case-control study using the tetra-Primer ARMS-PCR, as well as the sequencing method. Results: In total 29 SNPs of GSTM1 were identified by sequencing. Missense mutation occurred in the polymorphic loci of T1270533G and C1256088C. However, no evident relationships between the variant of T1270533G and clinical phenotypes of NPC were observed in the NPC group and healthy control group (OR=0.170, 95% CI = 0.95-0.306 for homozygote TT). The deletion frequency of C1256088C was 45% (45 / 100) for NPC patients and 42% (42 / 100) for controls. Conclusions: The polymorphism of T1270533G does not affect the detoxification function of GSTM1. The T1270533G locus has no apparent association with genetic susceptibility to NPC in the southern China population. The loss rate of C1256088C is high in this study.更多还原