Genome-wide DNA Methylation Profiling of CpG Islands in Hypospadias
Genome-wide DNA Methylation Profiling of CpG Islands in Hypospadias
复制标题
DOI：
10.1016/j.juro.2012.03.047
复制
发表时间：
2012-10-01
影响因子：
6.6
通讯作者：
Baskin, Laurence S.
中科院分区：
文献类型：
--
作者：
Choudhry, Shweta;Deshpande, Archana;Baskin, Laurence S.
目的：尿道下裂是男性新生儿最常见的生殖器畸形之一，是阴茎和尿路发育异常的结果。尽管进行了深入的研究，但尿道下裂的病因在很大程度上仍不清楚。胎儿雄激素在生殖器分化中起着至关重要的作用。最近的研究表明，雄激素对胎儿影响的分子机制可能涉及到发育过程中基因表达的表观遗传程序中断。在一项病例对照研究中，我们评估了DNA甲基化的表观遗传修饰是否与尿道下裂有关。材料和方法：使用Illumina Infinium(R)HumanMethylation450 BeadChip对研究对象进行全基因组DNA甲基化分析，这使得直接调查整个基因组中超过485,000个CpG位点的甲基化状态成为可能。用t检验和Logistic回归分析比较病例组和对照组各CpG位点的甲基化水平。
Purpose: Hypospadias is one of the most frequent genital malformations in the male newborn, and results from abnormal penile and urethral development. The etiology of hypospadias remains largely unknown despite intensive investigations. Fetal androgens have a crucial role in genital differentiation. Recent studies have suggested that molecular mechanisms that underlie the effects of androgens on the fetus may involve disruption of epigenetic programming of gene expression during development. We assessed whether epigenetic modification of DNA methylation is associated with hypospadias in a case-control study of 12 hypospadias and 8 control subjects.Materials and Methods: Genome-wide DNA methylation profiling was performed on the study subjects using the Illumina Infinium (R) HumanMethylation450 BeadChip, which enables the direct investigation of methylation status of more than 485,000 individual CpG sites throughout the genome. The methylation level at each CpG site was compared between cases and controls using the t test and logistic regression.Results: We identified 14 CpG sites that were associated with hypospadias with p