HDAC3基因在β-地中海贫血中甲基化状态及其意义研究  

Study on hypermethylation of gene HDAC3 in β-thalassemia

作　　者：高天[1] 梁志清[1] 聂艳丽[2] 张亮[2] 朱虹琳[2] 吴伟静[2] 胡华[1] 

机构地区：[1]第三军医大学西南医院妇产科,重庆400038 [2]生物芯片北京国家工程研究中心,102206

出　　处：《重庆医学》2009年第23期2957-2959,2962,I0004,共5页Chongqing medicine

基　　金：国家自然科学基金资助项目(30901619)

摘　　要：目的通过寡核苷酸芯片寻找和分析β-地中海贫血DNA甲基化相关的基因位点,进一步探讨早期诊断β-地中海贫血的新方法。方法利用含有人30178个DNA甲基化探针的寡核苷酸芯片,对2例β地中海贫血患儿脐血与2例正常脐血分别配对检测差异基因DNA甲基化情况,并用甲基化特异PCR(MSP)和DNA荧光定量PCR验证芯片结果。结果两组芯片结果显示,差异基因共209条(ratio≥2.0or≤0.50);其中上调基因共113条,下调基因共96条。验证结果显示,DNA甲基化相关基因组蛋白甲基转移酶3(HDAC3)与正常血样比较呈高甲基化状态。结论高通量的DNA甲基化基因芯片技术能够筛选出大量的地中海贫血差异表达基因,DNA甲基化相关基因HDAC3在地中海贫血中呈高甲基化。预示着利用DNA甲基化芯片分析地中海贫血中甲基化特异相关分子的规律和特点为临床上早期诊断地中海贫血开拓了新的思路和方法。Objective To search and analyze the DNA methylation-related genes of β-thalassemla by oligonucleotide microarray, to study the new method further for early diagnosis of β-thalassemia. Methods Two cases of children cord blood with β-thalassemia and two cases of normal cord blood were detected by containing human DNA methylation 30,178 oligonucleotide probe chips, and verifying the chip results by the methods of methylation-specific PCR （MSP） and DNA Realtime PCR. Results A total of 209 genetic differences （ratio ≥ 2.0 or ≤ 0. 50）were showed by two groups of chips, of them 113 genes were up-regulated and 96 genes were down-regulated. The results showed that DNA the methylation-related gene HDAC3 was hypermethylation compared with the normal blood. Conclusion A large number of differentially expressed genes were screened out by the technology of Highthroughput DNA methylation of the gene chip in thalassemia,the DNA methylation-related gene of HDAC3 was hypermethylation in thalassemia. It is prognosticated that a new idea and method are opened up for prenatal diagnosis in thalassemia by the method of DNA methylation-related microarry.

关 键 词：Β-地中海贫血 DNA甲基化 HDAC3 寡核苷酸芯片 MSP 

分 类 号：R556.61[医药卫生—血液循环系统疾病] R446.61[医药卫生—内科学]