DNA methylation variability in a pilot study group with ischemic stroke. Homo sapiens

Elevated plasma homocysteine is an independent risk factor for cardiovascular disease and stroke, however the etiology remains poorly understood. Elevated homocysteine is known to inhibit methyltransferases including DNA methyltransferases, but no methylome-wide analysis of elevated homocysteine has been reported. Peripheral blood genomic DNA methylation in 8 Singaporean-Chinese ischemic stroke patients (4 male, 4 female) with varying homocysteine titer and hypertensive status were profiled using methyl-CpG binding domain (MBD) protein-enriched genome sequencing (MBD-seq) on Illumina Genome Analyzer IIx. A methylome wide screen was undertaken for gender, total plasma homocysteine, hypertension and age. The data show considerable variability within the small cohort, including at genes which are related to one carbon metabolism and cardiovascular disease. Overall design: Peripheral blood genomic DNA methylation in 8 Singaporean-Chinese ischemic stroke patients (4 male, 4 female) was profiled using methyl-CpG binding domain (MBD) protein-enriched genome sequencing (MBD-seq) on Illumina Genome Analyzer IIx. Methylation parrterns were correlated with homocysteine levels, lypertensive status, gender and age.

血浆同型半胱氨酸（plasma homocysteine）水平升高是心血管疾病与脑卒中的独立危险因素，但其致病机制仍未得到充分阐明。现有研究表明，高同型半胱氨酸血症可抑制包括DNA甲基转移酶（DNA methyltransferases）在内的多种甲基转移酶，但目前尚无针对高同型半胱氨酸血症的全甲基化组分析相关报道。
本研究采用基于Illumina Genome Analyzer IIx平台的甲基化CpG结合域（methyl-CpG binding domain, MBD）蛋白富集基因组测序（MBD-seq）技术，对8名血浆同型半胱氨酸水平与高血压状态存在差异的新加坡华裔缺血性脑卒中患者（4男4女）的外周血基因组DNA甲基化水平进行了检测。随后针对性别、血浆总同型半胱氨酸水平、高血压状态及年龄开展了全甲基化组筛选。本次数据集的小样本队列中存在显著的甲基化水平异质性，涉及一碳代谢与心血管疾病相关基因。
整体实验设计：采用基于Illumina Genome Analyzer IIx平台的MBD-seq技术，对8名新加坡华裔缺血性脑卒中患者（4男4女）的外周血基因组DNA甲基化水平进行检测，并将甲基化模式与同型半胱氨酸水平、高血压状态、性别及年龄进行关联分析。