DNA methylation of NOS genes and carotid intima-media thickness in children

Carotid intima-media thickness, a biomarker for atherosclerosis, is associated with cardiovascular disease risk in adults. Atherosclerosis is a lifelong process that begins in childhood. Nitric Oxide (NO) plays an important role in cardiovascular health by maintaining and regulating vascular tone and blood flow. It remains unclear as to how the epigenetic regulation of nitric oxide synthase, the gene responsible for nitric oxide production, affects carotid intima-media thickness (CIMT) in children. Data from a subset of 377 participants from the Children’s Health Study on whom buccal cell DNA and CIMT measurements were collected were analyzed to determine whether DNA methylation in NOS genes was associated with CIMT. Results showed that an increase in DNA methylation of NOS1 was significantly associated with an increase in CIMT measurements in children. Our study suggests that DNA methylation of NOS genes is associated with CIMT in children, which may help to advance the understanding of biological processes contributing to atherosclerosis even at an early age.颈动脉内膜中层厚度（carotid intima-media thickness, CIMT）作为动脉粥样硬化的生物标志物，与成人心血管疾病风险密切相关。动脉粥样硬化是一种始于儿童时期的终身性病理进程。一氧化氮（nitric oxide, NO）可通过维持与调节血管张力及血流，在心血管健康中发挥重要作用。目前，负责合成一氧化氮的一氧化氮合酶基因的表观遗传调控，如何影响儿童颈动脉内膜中层厚度（CIMT）仍不明确。本研究对儿童健康研究（Children’s Health Study）中377名采集了颊细胞DNA并完成CIMT检测的受试者亚组数据进行分析，以明确NOS基因的DNA甲基化水平是否与CIMT存在关联。结果显示，儿童体内NOS1基因的DNA甲基化水平升高，与CIMT检测值升高呈显著正相关。本研究表明，儿童体内NOS基因的DNA甲基化水平与CIMT存在关联，这或有助于深化对早年即参与动脉粥样硬化发生发展的生物学进程的认知。