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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 elucidate the genotypic distribution of cytochrome P450-3A4 (CYP3A4) in Chinese children with acute leukemia (AL) and healthy children and to explore the possible association between CYP3A4 polymorphism and childhood leukemia susceptibility and chemotherapeutic effect. Methods The genotypes of CYP3A4 in 120 cases of AL and 85 healthy children were detected by PCR-RFLP and DNA sequencing. The genotype differences of CYP3A4 between the two groups were analyzed. Results Only one of the 85 healthy children had heterozygous genotypes of CYP3A4 * 1B, all of which were wild type. The frequency of heterozygous mutation was 1.2%. Among 120 AL children, 5 (4 ALL and 1 AML) The heterozygous heterozygous genotypes were heterozygous genotypes. One case of ALL was homozygote genotype. The heterozygous genotype mutation rate was 4.2%, and the homozygote genotype mutation rate was 0.8%. The results of PCR-RFLP and DNA sequencing showed that all subjects were wild-type CYP3A4 * 3 genotypes. Conclusions Although the mutation rate of CYP3A4 * 1B gene in children with AL is higher than that in healthy children, there is no significant difference. Therefore, it is impossible to conclude that the CYP3A4 * 1B genotype is associated with AL in Chinese children. CYP3A4 * 3 gene is a rare allele in Chinese healthy children and AL children. The effect of CYP3A4 * 3 on CYP3A4 activity and its role in leukemia remains to be further explored.