CYP1A1和CYP2D6基因多态性对白血病发生的影响

Genetic polymorphisms of CYP1A1 and CYP2D6 and their impact on leukemia morbidity

目的分析细胞色素P450 CYP1A1和CYP2D6的多态性基因型在湖南地区白血病患者和健康人群中的分布及其对白血病发生的影响。方法采用PCR及PCR-RFLP技术分析多态性基因型频率。结果CYP1A1和CYP2D6基因的野生型、杂合突变型及纯合突变型的分布频率在急性淋巴细胞性白血病、急性非淋巴细胞性白血病、慢性粒细胞性白血病患者组与健康对照组之间无显著性差异;携带一个突变等位基因型的个体患白血病的风险与相应野生型携带者比较均无显著性差异;急性非淋巴细胞性白血病患者组的CYP1A1杂合突变型与CYP2D6杂合突变型的联合基因型频率高于健康对照组。结论单独的CYP1A1或CYP2D6基因的多态性变异与白血病易感性不相关;CYP1A1杂合突变与CYP2D6杂合突变的联合基因型增加患急性非淋巴细胞性白血病的风险。

Objective To study the correlations between genetic polymorphisms of cytochrome P450 CYP1A1 and CYP2D6 and leukemia predisposition through investigating the frequency distributions of genetic polymorphisms of CYP1A1 and CYP2D6 in leukemia patients and healthy controls in the population of Hunan Province in China, Methods The frequencies of polymorphic genotypes of CYP1A1 and CYP2D6 were detected by PCR and PCR-RFLP technologies, Results Frequencies of the wild （W/W）, the heterozygous mutation （W/M） and the homozygous mutation （M/M） types of both CYP1A1 and CYP2D6 genes showed no significant differences among the patients with acute lymphoblastic leukemia （ALL）, acute non-lymphoblastic leukemia （ANLL） or chronic myelogenous leukemia （CML） and healthy controls. The individuals with W/M or M/M genotypes of CYP1A1 or CYP2D6 didn＇ t show increased leukemia risk over their wild type counterparts. However, the frequency of CYP1A1 W/M genotype combined with CYP2D6 W/M genotype of ANLL group was higher than that of the control group. Condusion The polymorphic variation of CYPIAI alone or of CYP2D6 alone does not affect the suscepti- bility to leukemia. However, heterozygous mutation of CYP1A1 gene combined with that of CYP2D6 gene increases the risk of ANLL.