中国急性白血病儿童的细胞色素P450-3A4基因型多态性分析

Analysis of Cytochrome P450 Genotype Polymorphism in Chinese Children with Acute Leukemia

目的阐明中国急性白血病(AL)和健康儿童中细胞色素P450-3A4(CYP3A4)的基因型分布特点,探讨CYP3A4基因型多态性与儿童白血病的易感性及化疗效应之间可能的相关性。方法应用PCR-RFLP及DNA测序法检测120例AL和85例健康儿童的CYP3A4基因型,分析两组CYP3A4基因型差异。结果85例健康儿童中仅1例为CYP3A4*1B的杂合子基因型,均为野生型,杂合子型的突变频率为1.2%;120例AL儿童中5例(4例ALL和1例AML)表现为杂合子基因型,1例ALL为纯合子基因型,其杂合子基因型突变率为4.2%,纯合子基因型突变率为0.8%。经PCR-RFLP检测并经DNA测序验证,所有受检者的CYP3A4*3基因型均为野生型。结论虽然AL患儿的CYP3A4*1B基因突变率高于健康儿童,但差异无显著性,因此尚不能推论CYP3A4*1B基因型与中国儿童AL发病相关。CYP3A4*3基因在中国健康和AL儿童中是一种罕见的等位基因,其对于CYP3A4酶活性的影响及其在白血病发生中的作用有待进一步探讨。

Objective To study the frequency distribution patterns of genotype polymorphism of the cytochrome P450-3A4 gene(CYP3A4)in Chinese children with acute leukemia and healthy control , to explore whether CYP3A4 mutation is related to vulnerability to childhood leukemia and the response to chemotherapy. Methods PCR-RFLP and DNA sequencing were used to detect genotypic polymorphism in 120 children with acute leukemia and 85 healthy children (control group), then the distribution of the genotypes was compared between the two groups. Results In 85 healthy children, only one child was heterozygotic genotype of CYP3A4 *1B, others were all wild type, the mutation frequency of heterozygote was 1.2%. While in 120 children with acute leukemia, five children (including four ALL and one AML) presented heterozygotic genotype of CYP3A4 *1B, one ALL child was homozygote genotype, the mutation frequency of heterozygote was 4.2% and the frequency of homozygote was 0.8%.Proved by PCR-RFLP and DNA sequencing,the genotype of CYP3A4 *3 was wild type in all subjects.Conclusions Although the mutation frequency of CYP3A4 *1B in children with acute leukemia is higher than that of in healthy control, there is no significance, thus it can not infer that the genotype of CYP3A4 *1B is correlated with the leukemogenesis in Chinese children. CYP3A4 *3 gene is a rare allele in Chinese healthy children and children with leukemia, its effect on CYP3A4 activity and leukemogenesis remains to further investigation.