摘要:
探讨雌激素受体2基因(Estrogen Receptor beta,ESR2)的表观遗传修饰作用与孤独症发病的关联性,为孤独症的病因学研究提供依据.方法 收集哈尔滨医科大学儿童发育行为研究中心的孤独症男性患儿54例,并按年龄-性别匹配原则随机收集正常对照男性儿童54名,运用亚硫酸盐测序法(Bisulfite Sequencing PCR,BSP)检测外周血细胞ESR2基因5,近端调控区的DNA甲基化.通过Mann-Whitney U检验比较病例组和对照组的DNA甲基化水平.结果 ESR2基因5,近端调控区的整体甲基化水平在孤独症组和对照组间的差异无统计学意义(P>0.05),但启动子区甲基化岛(Prom CGI)所包含的15个CpG位点中,有7个位点(CpG 5,6,8,9,10,11和12)的甲基化水平在孤独症组明显升高(P值均<0.05),部分位点存在于转录因子结合位点的保守序列中,包括USF2,ZBTB33,REL,ESR2和TFEC.此外,外显子区甲基化岛(Exon CGI)包含26个CpG位点,其中CpG41位点的甲基化水平在孤独症组(31.30±2.74)%高于对照组(24.07±2.59)%(P<0.05).结论 ESR2基因5’近端调控区的表观遗传修饰与孤独症的发病有明显关联.
Abstract:
Objective A case-control study was performed to explore the association between DNA methylation statue of the Estrogen Receptor Beta (ESR2) gene and autism,which could imply an evidence of autism etiology.Methods A random sample of 54 boys with autism and 54 normal boys was performed DNA methylation in 5' regulatory region of the ESR2 gene by Bisulfite Sequencing PCR.The different DNA methylation between autism and control was compared by Mann-Whitney U-test.Results The DNA methylation of the entire 5' regulatory region in the ESR2 gene showed no difference between autism and control (P>0.05).Prom CGI contains 15 CpG sites,in which 7 CpG sites (CpG 5,6,8,9,10,11 and 12) were hypermethylation in the autism group (P<0.05).Most of these sites were in the motifs for transcription factor binding sites,including USF2,ZBTB33,REL,ESR2 and TFEC.Among 26 CpG sites in the Exon CGI,CpG 41 was hypermethylation in the autism group (P<0.05).Conclusion The present study provides insight into the common genetic variation in ESR2 gene in autism through an epigenetic mechanism.
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