Department of Nutrition, Food Sciences and Physiology, University of Navarra, Pamplona, Spain.
J Physiol Biochem. 2014 Jun;70(2):603-14. doi: 10.1007/s13105-014-0316-5. Epub 2014 Feb 7.
Some causal bases of stroke remain unclear, but the nutritional effects on the epigenetic regulation of different genes may be involved. The aim was to assess the impact of epigenetic processes of human tumor necrosis factor (TNF-α) and paraoxonase (PON) promoters in the susceptibility to stroke when considering body composition and dietary intake. Twenty-four patients (12 non-stroke/12 stroke) were matched by sex (12 male/12 female), age (mean 70 ± 12 years old), and BMI (12 normal-weight/12 obese; mean 28.1 ± 6.7 kg/m(2)). Blood cell DNA was isolated and DNA methylation levels of TNF-α (-186 to +349 bp) and PON (-231 to +250 bp) promoters were analyzed by the Sequenom EpiTYPER approach. Histone modifications (H3K9ac and H3K4me3) were analyzed also by chromatin immunoprecipitation in a region of TNF-α (-297 to -185). Total TNF-α promoter methylation was lower in stroke patients (p < 0.001) and showed no interaction with body composition (p = 0.807). TNF-α and PON total methylation levels correlated each other (r = 0.44; p = 0.031), especially in stroke patients (r = 0.72; p = 0.008). The +309 CpG methylation site from TNF-α promoter was related to body weight (p = 0.027) and the region containing three CpGs (from -170 to -162 bp) to the percentage of lipid intake and dietary indexes (p < 0.05) in non-stroke patients. The methylation of PON +15 and +241 CpGs was related to body weight (p = 0.021), waist circumference (p = 0.020), and energy intake (p = 0.018), whereas +214 was associated to the quality of the diet (p < 0.05) in non-stroke patients. When comparing stroke vs non-stroke patients regarding the histone modifications analyzed at TNF-α promoter, no changes were found, although a significant association was identified between circulating TNF-α level and H3K9ac with H3K4me3. TNF-α and PON promoter methylation levels could be involved in the susceptibility to stroke and obesity outcome, respectively. The dietary intake and body composition may influence this epigenetic regulation in non-stroke patients.
一些中风的病因仍然不清楚，但营养对不同基因的表观遗传调控的影响可能与之相关。本研究旨在评估考虑人体成分和饮食摄入时，人类肿瘤坏死因子 (TNF-α) 和对氧磷酶 (PON) 启动子的表观遗传过程对中风易感性的影响。24 名患者（12 名非中风/12 名中风）按性别（12 名男性/12 名女性）、年龄（平均 70±12 岁）和 BMI（12 名正常体重/12 名肥胖；平均 28.1±6.7kg/m2）进行匹配。分离血细胞 DNA，通过 Sequenom EpiTYPER 方法分析 TNF-α（-186 至 +349bp）和 PON（-231 至 +250bp）启动子的 DNA 甲基化水平。还通过染色质免疫沉淀分析 TNF-α （-297 至 -185）区域中的组蛋白修饰（H3K9ac 和 H3K4me3）。中风患者的 TNF-α 启动子总甲基化水平较低（p<0.001），且与人体成分无交互作用（p=0.807）。TNF-α 和 PON 总甲基化水平相互关联（r=0.44；p=0.031），尤其是在中风患者中（r=0.72；p=0.008）。TNF-α 启动子的 +309 CpG 甲基化位点与体重相关（p=0.027），包含三个 CpG （从 -170 至 -162bp）的区域与脂质摄入量和饮食指数相关（p<0.05）。非中风患者中，PON +15 和 +241 CpG 的甲基化与体重（p=0.021）、腰围（p=0.020）和能量摄入（p=0.018）相关，而 +214 与饮食质量（p<0.05）相关。比较中风患者和非中风患者在 TNF-α 启动子上分析的组蛋白修饰时，未发现变化，但循环 TNF-α 水平与 H3K9ac 和 H3K4me3 之间存在显著关联。TNF-α 和 PON 启动子的甲基化水平可能分别参与中风和肥胖的易感性。饮食摄入和人体成分可能会影响非中风患者的这种表观遗传调控。
