NOS1 methylation and carotid artery intima-media thickness in children.
NOS1 methylation and carotid artery intima-media thickness in children.
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DOI：
10.1161/circgenetics.113.000320
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发表时间：
2014-04
期刊：
影响因子：
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通讯作者：
Gilliland FD
中科院分区：
文献类型：
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作者：
Breton CV;Park C;Siegmund K;Gauderman WJ;Whitfield-Maxwell L;Hodis HN;Avol E;Gilliland FD
一氧化氮（NO）通过维持和调节血管张力和血流在心血管健康中起重要作用。一氧化氮合酶（NOS）的表观遗传调控可能影响心血管疾病，包括儿童动脉粥样硬化的发展。我们使用亚硫酸盐转化和焦磷酸测序测定来自377名儿童健康研究参与者提供的颊细胞DNA的DNA甲基化百分比，这些参与者也收集了颈动脉内膜-中膜厚度（CIMT）测量数据。我们共检测了位于NOS1、NOS2A、NOS3、ARG1和ARG基因中的16个CpG位点，这些基因负责NO的产生。采用高分辨率b型颈动脉超声测量CIMT。采用线性回归评估ARG和NOS基因甲基化百分比与CIMT之间的关系，调整性别、种族、体重指数、CIMT年龄、居住城镇和焦焦测序反应实验板。不同种族和祖先群体的关联差异也进行了评估。NOS1 DNA甲基化水平每增加1%，CIMT增加1.2 μm （p=0.02）。与非西班牙裔白人（β =0.3, p=0.71）或西班牙裔白人（β = 1.0, p=0.35）相比，美洲原住民后裔的西班牙裔儿童（β = 2.3, p=0.004）的相关性更大。NOS1的DNA甲基化通过调节NO的产生在动脉粥样硬化中起着合理的作用，尽管祖先可能会改变这种关联的程度。
Nitric oxide (NO) plays an important role in cardiovascular health by maintaining and regulating vascular tone and blood flow. Epigenetic regulation of nitric oxide synthase (NOS), the genes responsible for NO production, may affect cardiovascular disease including development of atherosclerosis in children. We measured percentage DNA methylation using bisulfite conversion and Pyrosequencing assays on DNA from buccal cells provided by 377 participants of the Children’s Health Study on whom carotid artery intima-media thickness (CIMT) measurements were also collected. We examined a total of 16 CpG loci located within NOS1, NOS2A, NOS3, ARG1 and ARG, genes responsible for NO production. CIMT was measured using high-resolution B-mode carotid ultrasound. The association between percentage DNA methylation in ARG and NOS genes with CIMT was evaluated using linear regression adjusted for sex, Cethnicity, body mass index, age at CIMT, town of residence and experimental plate for pyrosequencing reactions. Differences in the association by ethnicity and ancestral group were also evaluated. For a 1% increase in average DNA methylation of NOS1, CIMT increased by 1.2 μm (p=0.02). This association was greater in Hispanic children of Native American descent (β = 2.3, p=0.004) than in Non-Hispanic Whites (β = 0.3, p=0.71) or Hispanic Whites (β = 1.0, p=0.35). DNA methylation of NOS1 has a plausible role in atherogenesis through regulation of NO production, though ancestry may alter the magnitude of this association.