HOXA5基因转录起始点上游区域高甲基化水平与神经管缺陷的关系
发布时间：2019-05-11 21:53
【摘要】：目的探讨同源异形盒基因转录起始点(TSS)上游区域甲基化水平与神经管缺陷(NTDs)的关系。方法采用两阶段病例对照研究设计。第一阶段选择NTDs病例10例和对照8例作为研究对象,运用全基因组甲基化芯片检测其脑或脊髓DNA全基因组甲基化水平。针对HOXA5基因差异甲基化区域,在第二阶段扩大样本量(52例病例和23例对照)进行验证。提取脑或脊髓组织DNA,使用Mass ARRAY系统的基质辅助激光解吸电离飞行时间质谱技术对HOXA5基因差异性甲基化区域进行验证。结果第一阶段在全基因组甲基化芯片结果中筛选出HOXA5基因TSS上游区27个CpG位点在病例组甲基化水平高于对照组(P0.05)。第二阶段利用Mass ARRAY系统针对上述发现的差异区域进行检测,成功检测到10个可用于分析CpG位点。NTDs病例组及其亚型脊柱裂组和无脑畸形组中甲基化水平高于对照组的CpG位点数各有7、6和2个(P0.005)。HOXA5基因TSS上游区域病例组平均甲基化水平高于对照组[NTDs病例组:(31.3±13.9)%,对照组:(21.4±9.7)%],调整胎儿性别和孕周后OR值为1.09(1.03~1.16)。结论 HOXA5基因TSS上游区域高甲基化与胎儿神经管缺陷风险增加存在关联性。
[Abstract]:Objective to investigate the relationship between the level of methylation in the upstream region of (TSS) and neural tube defect (NTDs) at the transcriptional initiation point of homeobox gene. Methods A two-stage case-control study was designed. In the first stage, 10 cases of NTDs and 8 cases of control were selected as the subjects, and the whole genome methylated level of DNA in brain or spinal cord was detected by whole genome methylating chip. According to the differentially methylated region of HOXA5 gene, the sample size (52 cases and 23 controls) was expanded in the second stage. DNA, was extracted from brain or spinal cord tissue by matrix-assisted laser desorption ionization time-of-flight mass spectrometry with Mass ARRAY system to verify the differentially methylated region of HOXA5 gene. Results in the first stage, 27 CpG loci in the upstream region of HOXA5 gene TSS were screened out from the whole genome methylated chip results, and the methylation level in the case group was higher than that in the control group (P 0.05). In the second stage, the Mass ARRAY system is used to detect the difference areas found above. Ten CpG loci were successfully detected for the analysis of CpG loci. The number of CpG loci in NTDs case group and its subtypes of spina bifida group and anencephalic malformation group were 7, 6 and 2, respectively (P0.005). The upstream region of TSS of NTDs gene was 7, 6 and 2 (P0.005), respectively, which could be used to analyze NTDs and its subtypes of spina bifida and cerebral malformation. The average methylated level in the case group was higher than that in the control group [NTDs case group: (31.3 卤13.9)%, In the control group: (21.4 卤9.7)%, the adjusted fetal sex and OR value after gestational age were 1.09 (1.03 鈮，
本文编号：2474880
[Abstract]:Objective to investigate the relationship between the level of methylation in the upstream region of (TSS) and neural tube defect (NTDs) at the transcriptional initiation point of homeobox gene. Methods A two-stage case-control study was designed. In the first stage, 10 cases of NTDs and 8 cases of control were selected as the subjects, and the whole genome methylated level of DNA in brain or spinal cord was detected by whole genome methylating chip. According to the differentially methylated region of HOXA5 gene, the sample size (52 cases and 23 controls) was expanded in the second stage. DNA, was extracted from brain or spinal cord tissue by matrix-assisted laser desorption ionization time-of-flight mass spectrometry with Mass ARRAY system to verify the differentially methylated region of HOXA5 gene. Results in the first stage, 27 CpG loci in the upstream region of HOXA5 gene TSS were screened out from the whole genome methylated chip results, and the methylation level in the case group was higher than that in the control group (P 0.05). In the second stage, the Mass ARRAY system is used to detect the difference areas found above. Ten CpG loci were successfully detected for the analysis of CpG loci. The number of CpG loci in NTDs case group and its subtypes of spina bifida group and anencephalic malformation group were 7, 6 and 2, respectively (P0.005). The upstream region of TSS of NTDs gene was 7, 6 and 2 (P0.005), respectively, which could be used to analyze NTDs and its subtypes of spina bifida and cerebral malformation. The average methylated level in the case group was higher than that in the control group [NTDs case group: (31.3 卤13.9)%, In the control group: (21.4 卤9.7)%, the adjusted fetal sex and OR value after gestational age were 1.09 (1.03 鈮，
本文编号：2474880
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