细胞色素P450 3A4基因多态性及与肝癌易感性研究

Genetic polymorphism of Cytochrome P450 3A4 and susceptibility to hepatocellular carcinoma

目的 探讨细胞色素P450 3A4.(CYP3A4)基因的多态性与肝癌的关系。方法应用聚合酶链反应(PCR)、变性梯度凝胶电泳(DGGE)、单链构象多态(SSCP)和DNA测序技术,对84例肝癌患者和144例健康对照的CYP3A4基因的多态性进行了研究。结果通过对CYP3A4基因10个外显子的检测,发现2例肝癌患者的第7外显子第15742位核苷酸发生了A—G转换,使得第183位氨基酸残基由天冬酰胺转变为丝氨酸;发现第10内含子存在一单核苷酸多态,表现第20338位核苷酸发生了G→A转换。病例组G/G、G/A和A/A基因型频率分别为59.52％,36.90％和3.58％;对照组则为59.72％,33.33％和6.95％。两组比较没有统计学差异。结论CYP3A4基因可能高度保守,虽有突变,但属罕见。

Objective To study the genetic polymorphisms of cytochrome P450 3A4 (CYP3A4) and the relationship between polymorphisms and susceptibility to hepatocellular carcinoma (HCC). Methods The polymorphisms of CYP3A4 in 84 patients with HCC and 144 healthy controls were detected by PCR-DGGE-Sequence or PCR-SSCP-Sequence. Results Ten exons of CYP3A4 were tested. In 2 cases a transition of A→G at nucleotide 15742 in exon 7 of CYP3A4 was found, this change led to an asparagine at 183rd residue substituted by a serine. A single nucleotide polymorphism (SNP) of transition G→A at nucleotide 20338 was found in intron 10,The frequencies of G/G,G/A and A/A genotypes of cases were 59.52% ,36.90% and 3.58% respectively, while those of controls were 59.72%,33.33% and 6.95% respectively. The difference was not statistically significant. Conclusion CYP3A4 may be a highly conservative gene, mutation is very rare.