原因不明复发性流产绒毛DNA全基因组甲基化芯片结果的分析  

Analysis on methylation microarrays of villus genome of unexplained recurrent miscarriage

作　　者：马天仲[1] 牛艳茹[2] 韦冰[1] 陈碧[1] 彭彩玲[1] 荆霞[1] 张云山[1] 邹琳[1] 车小群[1] 庞小艳[1] 许丽华[1] 

机构地区：[1]广东医学院附属医院生殖医学中心,广东湛江524001 [2]广东医学院微创骨科研究室,广东湛江524001

出　　处：《广东医学院学报》2015年第6期661-664,共4页Journal of Guangdong Medical College

基　　金：国家自然科学基金(No.81300484);湛江市财政资金科技专项竞争性分配项目(No.2013A01006);广东医学院博士启动基金(No.B2012027)

摘　　要：目的分析原因不明复发性流产与人工终止妊娠绒毛中DNA甲基化450k芯片结果的差异情况。方法收集原因不明复发性流产绒毛3例作为实验组(A组),人工终止妊娠绒毛3例作为对照组(B组);用Illumina Infinium Human Methylation 450 Bead Array芯片,在单核苷酸水平上评估胚胎绒毛DNA约485 000个Cp G位点的甲基化情况,并对甲基化表达差异基因进行生物信息学分析。结果 A组与B组Cp G甲基化位点差异为1 768个(623个高甲基化位点,1 145个低甲基化位点);两组样本在基因的TSS1500、TSS200、5'UTR、1st Exon、Gene body和3'UTR内差异甲基化区域个数为35、36、28、26、34、25;而在Cp G Island、N shelf、N Shore、S shore和S Shelf内差异甲基化区域个数为58、52、72、54、67。生物信息学分析差异Cp G位点所在基因和差异甲基化区域身份和功能;这些基因位点主要与胚胎肢体发育、神经细胞凋亡和增殖、免疫应答调节和炎症反应等密切相关。结论胚胎绒毛甲基化表观异常的改变可能是导致原因不明复发性流产发生的重要因素。Objective To study the differences in villus DNA methylation 450 k microarray between unexplained recurrent miscarriage and pregnancy termination. Methods Villi of three cases with unexplained recurrent miscarriage were collected as experimental group（Group A）,and those of three cases with pregnancy termination were collected as control group（Group B）. Illumina Infinium Human Methylation 450 Bead Array chip was used to evaluate methylation status of about 485 000 DNA Cp G sites of embryo villi based on single nucleotide level,and bioinformatics analysis was conducted on the differentially expressed methylation genes. Results Cp G methylation sites difference between Group A and Group B was 1 768（623 hypermethylation sites and 1145 hypomethylation sites）; the number of differential methylation regions of the two groups in TSS1500,TSS200,5＇UTR,1st Exon,Gene body and 3＇UTR number was： 35,36,28,26,34 and 25; while that in Cp G Island,N shelf,N Shore,S shore and S Shelf was： 58,52,72,54 and 67. Bioinformatics analysis was conducted for the genes where differential Cp G sites locate and the identity and function of differential methylation regions; these gene loca are mainly closely related to embryonic development,nerve cell apoptosis and proliferation,immune response and inflammatory reactions. Conclusion Abnormal methylation appearance in villus may be an important factor leading to the occurrence of unexplained recurrent spontaneous abortion.

关 键 词：复发性流产 绒毛 甲基化 芯片 

分 类 号：R711.6[医药卫生—妇产科学]