摘要
目的探讨急性白血病患者DNA修复基因(hMSH2和hMLH1基因)mRNA、蛋白表达情况及其启动子甲基化状态。方法选取56例急性白血病患者和30名健康志愿者,用反转录-聚合酶链反应(RT-PCR)和免疫印迹(western blot)检测其单个核细胞错配修复基因hMSH2和hMLH1的mRNA及蛋白表达,用甲基化特异性聚合酶链反应(MSP)法检测hMSH2和hMLH1启动子区甲基化状态。结果与健康志愿者组比较,急性白血病患者的错配修复基因hMSH2和hMLH1均明显低表达,差异有统计学意义(P<0.05);急性白血病患者hMSH2和hMLH1甲基化阳性率为66.1%(37/56)和55.4%(31/56),明显高于健康志愿者的10.0%(3/30)和6.7%(2/30),差异有统计学意义(P<0.05);急性白血病患者hMSH2和hMLH1表达与其甲基化状态呈负相关性(rhMSH2=-0.624,P=0.000;rhMLH1=-0.589,P=0.002)。结论急性白血病患者的hMSH2和hMLH1基因呈低表达,其启动子呈高甲基化水平,急性白血病患者hMSH2和hMLH1基因表达低下与其启动子甲基化状态有关。
Objective To explore the CpG island methylation of human Mut S homologue 1（hMLH1） and human Mut S homologue 2（hMSH2） gene and their expressions in acute leukemia patients.Methods Reverse transcription-polymerase chain reaction（RT-PCR）and western blot were used to measure hMSH2 and hMLH1 mRNA and protein expression.Methylation-specific polymerase chain reation（MSP） technique was adopted to detect methylation of hMLH1 and hMSH2 gene in mononuclear cells of 56 acute leukemia patients and 30 healthy volunteers.Results The mRNA and protein expression levels of hMSH2 and hMLH1 in mononuclear cells of acute leukemia patients decreased significantly compared with those of healthy volunteers（P0.05）.The frequency of promoter methylation of hMSH1and hMSH2 gene in mononuclear cells of 56 acute leukemia patients were 66.1%（37/56）and 55.4%（31/56）,respectively,while those frequencies in healthy volunteers were 10.0%（3/30）and 6.7%（2/30）.The differences between the two groups were statistically significant（P0.01）.There was a negative correlation between the CpG island methylation of hMLH1 and hMSH2 gene and their expressions in acute leukemia（rhMSH2=-0.624,P=0.000;rhMLH1=-0.589,P=0.002）.Conclusion There are low expressions of hMSH2 and hMLH1 gene and high methylation of hMLH1 and hMSH2 gene in acute leukemia patients.The CpG island methylation is a factor for the low expression phenomenon of hMSH2 and hMLH1 gene in acute leukemia patients.
出处
《中国公共卫生》
CAS
CSCD
北大核心
2011年第7期870-872,共3页
Chinese Journal of Public Health
基金
国家自然科学基金(30471644)
广东省自然科学基金重点项目(06112013)
