儿童急性白血病患者的谷胱甘肽S-转移酶Pi基因多态性分析  

Analysis on GST-Pi genetic polymorphism in children with acute leukemia

作　　者：袁晓军[1] 顾龙君[1] 薛惠良[1] 汤静燕[1] 赵金彩[1] 陈静[1,1] 王耀平[1] 陈静[1,1] 潘慈[1] 宋得莲 

机构地区：[1]上海第二医科大学附属新华医院上海儿童医学中心血液肿瘤科,200127

出　　处：《中华医学杂志》2003年第21期1863-1866,共4页National Medical Journal of China

基　　金：上海市科学技术发展基金项目 ( 9943 190 3 3)

摘　　要：目的　研究谷胱甘肽S 转移酶Pi(GST Pi)的基因型多态性在中国儿童急性白血病 (AL)中的频率分布特征 ,探讨GST Pi基因变异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　采用DNA直接测序法对 12 0例AL患儿和 85名健康儿童进行GST Pi基因型的测定 ,分析各基因型在AL儿童与健康对照者之间的分布差异。结果　AL患儿GST Pi外显子 5的突变率为 4 7 5 % ,明显高于健康儿童的 31 8% (OR =1 94 4 ,95 %CI为 1 0 88～ 3 4 73) ,其多态性分布特征与国外报道相似。其中 ,ALL患儿外显子 5的基因突变率增高更明显 ,而AML患儿与健康儿童的差异未达到显著水平 ;B系ALL患儿的总突变率 (6 0 3% )明显高于T ALL儿童 (4 7 1% ) ,但后者的纯合子突变率(17 6 % )显著高于前者 (3 4 % ) (P值均 <0 0 5 ) ;野生型ALL患儿的平均生存时间为 2 4个月 ,长于突变型患儿的 17 6个月 ,但差异未达到统计学意义 (P =0 0 80 4 ) ;外显子 5基因型对AML患儿的存活时间亦无显著影响。在所有受检儿童中 ,未发现GST Pi外显子 6存在文献报道的Ala114 Val变异基因型 ,但发现了两个新的突变基因型 :1例健康儿童的外显子 6第 99位点出现A/G杂合 ,该杂合基因型未引起氨基酸的改变 ;2例白血病儿童在外显子 6第 10 3测序位点发生G→T/G碱?Objectives To study the frequency distribution patterns of the genetic polymorphisms for glutathione S-transferase Pi(GST-Pi)in children with acute leukemia, and explore the possible relationship of GST-Pi gene mutation to the vulnerability of children with leukemia and the chemotherapeutic response. Method Direct DNA sequencing was applied to detect the genotype polymorphism in 85 healthy children as the control group and 120 children with acute leukemia. The distribution difference of the genotypes between them was analyzed. Results Gene mutation rate of GST-Pi exon5 was 47.5% in children with acute leukemia, significantly higher than that of 31.8% in the control group (OR=1.944, 95%CI 1.088～3.473), and this polymorphism distribution pattern was similar to that reported abroad. The mutation rate was much higher in ALL group than in others groups and was not significantly between the AML children and the control group. The overall mutation rate of B-lineage ALL (60.3%) was markedly higher than that of T-ALL (47.1%), but the homozygous mutation rate of the latter group (17.6%) was much higher than that of the former group (3.4%) (P<0.05). The average survival time of the children with wild type exon5 was 24 months, longer than that of the mutation group (17.6 months), however with no statistical difference (P>0.05). The genotype of exon5 had no effect on the survival time of AML children. No Ala 114Val variant genotype of GST-Pi exon6 reported in literatures was found in this study, but two new mutant genotypes were discovered. A/G hybridity at 99 loci of exon6 was found in one healthy child and such hybrid genotype did not result in amino acid alteration. G→T/G bases hybridity at 103 loci of exon6 occurred in two children with leukemia, leading to GAC of Asp (aspartic acid) replaced by TAC of Try (tyrosine) at 147 loci of the protein peptide chain, producing Asp 147 Try hybrid mutation with a genotypic frequency of 1.7%. Conclusion The gene mutation of GST-Pi exon5 is one of the potential vulnerable f

关 键 词：儿童 急性白血病 谷胱甘肽S-转移酶Pi 基因多态性 

分 类 号：R733.71[医药卫生—肿瘤]