细胞色素P4501A1、谷胱甘肽转硫酶基因多态性与儿童急性淋巴细胞白血病的相关性研究

Association between the polymorphisms of cytochrome P4501A1 and glutathione S-transferase M1, T1 Genes and childhood acute lymphocytic leukemia

目的探讨生物代谢酶细胞色素P4501A1、谷胱甘肽转硫酶M1、T1基因多态性与儿童急性淋巴细胞白血病(ALL)的相关性。方法采用病例对照研究方法,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术对89例儿童ALL患儿以及90名健康对照者的CYP1A1 Msp Ⅰ多态(T264C)、GSTMI和GSTT1等基因的多态分布进行分析。结果儿童ALL组的CYP1A1基因Msp Ⅰ多态纯合子突变型(C型)的频率与对照组差异有统计学意义(P<0.05),携带纯合子突变型的儿童患ALL的危险度比杂合子突变型(B型)与野生型(A型)儿童的高(OR=1.997,95% CI:1.024～3.896)。GSTM1缺失型分布频率与对照组相比差异有统计学意义(P<0.05,OR=2.709,95%CI:1.427～5.146),GSTT1缺失型分布频率与对照组相比差异无统计学意义(P>0.05)。同时携带CYPlAl C型、GSTM1、GSTT1缺失型的联合基因型儿童患ALL的风险增加(OR=2.235,95% CI:1.111～4.497)。结论 CYP1A1基因Msp Ⅰ多态纯合子突变型(C型)、GSTM1缺失型与儿童ALL的易感性可能相关,GSTT1缺失型与儿童ALL易感性可能不相关;同时携带CYP1A1 C型与GSTM1、GSTT1缺失基因型可能是儿童ALL发病的易感因素之一。

Objective To study the association between metabolic enzymes polymorphisms of eytochrome P4501A1 and glutathione S-transferase M1,T1 genotypes and childhood acute lymphocytic leukemia. Methods U- sing ease-control methodology, 90 healthy controls and 89 patients with childhoed ALL were studied. The frequencies of the genotypes were detected by PCR-RFLP techniques. Results Homozygous mutation（C） of CYP1A1 gene （Msp I pulymorphisms） between patients and healthy controls were statistically significant （P 〈0. 05） ,the risk of ALL in the individuals with homozygous mutation was higher than that in individuals with heterozygote（B） and wild type（A） （OR = 1. 997, 95% CI： 1. 024 - 3. 896）. The null genotype of GSTM1 in childhood ALL group was significantly different from that in the controls （ P 〈 0. 05, OR = 2. 709, 95% CI： 1. 427 - 5. 146 ）. The null genotype of GSTrl in childhood ALL group was not significantly different from that in the controls （P 〉 0. 05 ）. In the patients with homozygous mutation of CYPIA1 gene combined with the null genotype of GSTM1 ,GSTrl, the risk of childhood ALL was increased（ OR = 2. 235 , 95% CI：1. 111 -4.497）. Conclusion These results indicated that homozygous mutation of CYPIA1 gene and the nun genotype of GSTM1 alone might be associated with the susceptibility of childhood ALL. The null genotype of GSTrl alone might not be associated with the susceptibility of childhood ALL. Homozygous mutation of CYP1A1 gene combined with the null genotype of GSTM1,GSTT1 might serve as a risk factor in the etiology of childhood ALL.