Stojković Ljiljana, Zec Manja, Zivkovic Maja, Bundalo Maja, Bošković Maja, Glibetić Marija, Stankovic Aleksandra
Laboratory for Radiobiology and Molecular Genetics, Department of Health and Environmental Research, "Vinča" Institute of Nuclear Sciences-National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia.
Centre of Research Excellence in Nutrition and Metabolism, Institute for Medical Research-National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia.
Front Nutr. 2021 Jun 17;8:689055. doi: 10.3389/fnut.2021.689055. eCollection 2021.
Cardiovascular disease (CVD) is associated with alterations in DNA methylation and polyunsaturated fatty acid (PUFA) profile, both modulated by dietary polyphenols. The present parallel, placebo-controlled study (part of the original clinical study registered as NCT02800967 at www.clinicaltrials.gov) aimed to determine the impact of 4-week daily consumption of polyphenol-rich juice (AMJ) treatment on () methylation in peripheral blood leukocytes and on plasma PUFAs, in subjects ( = 54, age range of 40.2 ± 6.7 years) at moderate CVD risk, including an increased body mass index, central obesity, high normal blood pressure, and/or dyslipidemia. The goal was also to examine whether factors known to affect DNA methylation (folate intake levels, C677T gene variant, anthropometric and metabolic parameters) modulated the methylation levels upon the consumption of polyphenol-rich aronia juice. Experimental analysis of methylation was done by MethyLight method. C677T genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism method, and folate intake was assessed by processing the data from the food frequency questionnaire. PUFAs were measured by gas-liquid chromatography, and serum lipid profile was determined by using Roche Diagnostics kits. The statistical analyses were performed using Statistica software package. In the comparison after vs. before the treatment period, in dyslipidemic women ( = 22), we observed significant decreases in methylation levels (97.54 ± 1.50 vs. 98.39 ± 0.86%, respectively; = 0.01) and arachidonic acid/eicosapentaenoic acid ratio [29.17 ± 15.21 vs. 38.42 (25.96-89.58), respectively; = 0.02]. The change (after vs. before treatment) in methylation directly correlated with the presence of 677T allele, average daily folate intake, and the change in serum low-density lipoprotein cholesterol but inversely correlated with the change in serum triacylglycerols ( = 0.72, = 0.52, adjusted = 0.36, = 0.03). The current results imply potential cardioprotective effects of habitual polyphenol-rich aronia juice consumption achieved through the modifications of DNA methylation pattern and PUFAs in subjects at CVD risk, which should be further confirmed. Hence, the precision nutrition-driven modulations of both DNA methylation and PUFA profile may become targets for new approaches in the prevention of CVD.
心血管疾病(CVD)与DNA甲基化和多不饱和脂肪酸(PUFA)谱的改变有关,而这两者均受膳食多酚调节。本项平行、安慰剂对照研究(原始临床研究的一部分,在www.clinicaltrials.gov上注册为NCT02800967)旨在确定在中度CVD风险受试者(n = 54,年龄范围40.2±6.7岁)中,每日饮用富含多酚的果汁(AMJ)4周对其外周血白细胞中的()甲基化以及血浆PUFA的影响,这些受试者存在体重指数增加、中心性肥胖、血压高值和/或血脂异常等情况。研究目标还包括检验已知影响DNA甲基化的因素(叶酸摄入水平、C677T基因变体、人体测量和代谢参数)在饮用富含多酚的黑果腺肋花楸果汁后是否会调节()甲基化水平。甲基化的实验分析采用甲基化荧光定量法。C677T基因型通过聚合酶链反应-限制性片段长度多态性方法测定,叶酸摄入量通过处理食物频率问卷数据进行评估。PUFA采用气液色谱法测量,血清脂质谱通过使用罗氏诊断试剂盒测定。统计分析使用Statistica软件包进行。在治疗期前后的比较中,在血脂异常的女性(n = 22)中,我们观察到()甲基化水平显著降低(分别为97.54±1.50%和98.39±0.86%;P = 0.01)以及花生四烯酸/二十碳五烯酸比值降低[分别为29.17±15.21和38.42(25.96 - 89.58);P = 0.02]。()甲基化的变化(治疗后与治疗前相比)与C677T等位基因的存在、平均每日叶酸摄入量以及血清低密度脂蛋白胆固醇的变化直接相关,但与血清三酰甘油的变化呈负相关(r = 0.72,P = 0.52,校正r = 0.36,P = 0.03)。目前的结果表明,习惯性饮用富含多酚的黑果腺肋花楸果汁可能通过改变CVD风险受试者的DNA甲基化模式和PUFA而具有潜在的心脏保护作用,这一点有待进一步证实。因此,由精准营养驱动的DNA甲基化和PUFA谱的调节可能成为预防CVD新方法的靶点。