摘要
目的 :探讨中国南方汉族人群O6 甲基鸟嘌呤 DNA甲基转移酶 (MGMT)基因 5个外显子的多态性与肿瘤易感性的关系。方法 :采用聚合酶链式反应 (PCR) 单链构象多态性 (SSCP) DNA直接测序法对 10 0例正常人和 88例肿瘤患者外周血白细胞进行MGMT基因多态性研究。结果 :正常人群和肿瘤患者第 3外显子第 84位密码子的第 1个碱基C被T所取代 ,导致错义突变 (CTT→TTT) ,氨基酸由亮氨酸 (Leu)变成了苯丙氨酸 (Phe) ;第 4外显子第 94位密码子的第 3个碱基C被T所取代 ,导致同义突变 (TTC→TTT ,均编码Phe)。这 2个位点的多态性在 2组人群中的检出率差异不存在统计学意义 (P >0 .0 5 )。同时在肿瘤患者中还检测到MGMT基因第 5外显子第 2 0 0位密码子的第 2个碱基G被C取代 ,即GGC→GCC ,所编码的氨基酸由甘氨酸变为缬氨酸 ,这一多态不存在于正常对照中。结论 :MGMT基因第 3、4、5外显子上存在着多态性 ,其中第 3、4外显子的多态改变与肿瘤形成的关系较弱 ,而第 5外显子的多态仅见于肿瘤患者 ,可能与肿瘤的形成有关。
Purpose: To investigate the polymorphisms of exons 1～5 in human O+6-methylguanine-DNA methyltransferase (MGMT) gene and their relationship with the susceptibility to tumors. Methods: The polymorphisms of exons 1～5 were analyzed with polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) and DNA sequencing in 188 Chinese Han people (100 healthy people and 88 tumor patients). Results: A polymorphism of exon 3, a C-to-T missense mutation, was detected at the first base of codon 84 (CTT→TTT, Leu→Phe), and a polymorphism of exon 4, a C-to-T same sense mutation, was found at the third base of codon 94 (TTC→TTT, both encode Phe). There was no statistical significance of the polymorphisms of the two sites between the two groups (P<0.05). Besides, there was a missense mutation of exon 5 in the tumor people, that is, a G-to-C change of the second base at codon 200 (GGC→GCC, Gly→Ala). This polymorphism didn't exist in the normal people. Conclusion: There were the polymorphisms of exons 3,4 and 5 in MGMT gene. The relationship between the polymorphism of exon 3 or 4 and tumorigenesis might be weak. The polymorphism of exon 5 only existed in the tumor people, which indicated that the polymorphism might be correlated with carcinogenesis.
出处
《癌变·畸变·突变》
CAS
CSCD
2002年第2期101-106,共6页
Carcinogenesis,Teratogenesis & Mutagenesis
