Department of Preventive Medical Sciences, School of Medical Sciences, Fujita Health University, Toyoake, Japan.
Department of Hygiene, School of Medicine, Fujita Health University, Toyoake, Japan.
Am J Clin Nutr. 2019 Nov 1;110(5):1213-1219. doi: 10.1093/ajcn/nqz181.
Higher intake of fruits and vegetables is associated with reduced risk of specific types of cancer and of cardiovascular disease (CVD), but the protective role of the vitamins contained in fruits and vegetables on CVD is controversial. This discrepancy can raise the question of the effects of antioxidants in vitamins on CVD. Recently, we reported that higher vegetable intake was significantly associated with the decreased DNA methylation level of ATP-binding cassette transporter A1 (ABCA1), a gene associated with HDL-cholesterol metabolism.
We investigated whether ABCA1 DNA methylation mediates an effect of dietary vitamin intake on lipid profiles, an important risk factor for CVD, in a Japanese population.
A total of 225 individuals (108 men and 117 women) with no clinical history and no drug use for dyslipidemia participated in this cross-sectional study. We used the pyrosequencing method to measure the ABCA1 DNA methylation levels at 8 CpG sites, and we used mean DNA methylation level in statistical analysis. Dietary vitamin intake was assessed with the FFQ and adjusted for the residual method.
In women, higher dietary vitamin intake [vitamin A, β-carotene, folic acid, vitamin C (VC), vitamin D, and vitamin E] was significantly associated with lower mean ABCA1 DNA methylation levels (P = 0.004, 0.03, 0.005, 0.001, 0.03, and 0.04, respectively). In addition, in women, we found a significant inverse association between mean ABCA1 DNA methylation and HDL cholesterol (P = 0.04) but not for other lipid indexes. Mediation analysis showed a significant indirect effect of VC intake on HDL cholesterol through ABCA1 DNA methylation level in women (P = 0.04).
Although this study does not prove causality, the results suggest that ABCA1 DNA methylation mediates the protective effect of VC on HDL cholesterol in women, which could offer a novel biological mechanism in CVD prevention.
摄入更多的水果和蔬菜与降低某些类型的癌症和心血管疾病（CVD）的风险有关，但水果和蔬菜中所含维生素对 CVD 的保护作用仍存在争议。这种差异可能会让人质疑维生素中的抗氧化剂对 CVD 的影响。最近，我们报道称，蔬菜摄入量较高与载脂蛋白 A1（ABCA1）的 DNA 甲基化水平降低显著相关，ABCA1 是与高密度脂蛋白胆固醇代谢有关的基因。
我们在日本人群中研究了 ABCA1 DNA 甲基化是否介导了饮食维生素摄入对脂质谱的影响，脂质谱是 CVD 的一个重要危险因素。
共有 225 名无临床病史且未使用药物治疗血脂异常的个体（男性 108 名，女性 117 名）参与了这项横断面研究。我们使用焦磷酸测序法测量了 8 个 CpG 位点的 ABCA1 DNA 甲基化水平，并在统计分析中使用平均 DNA 甲基化水平。膳食维生素摄入量通过 FFQ 进行评估，并采用残差法进行调整。
在女性中，较高的膳食维生素摄入（维生素 A、β-胡萝卜素、叶酸、维生素 C（VC）、维生素 D 和维生素 E）与 ABCA1 DNA 甲基化水平的降低显著相关（P 值分别为 0.004、0.03、0.005、0.001、0.03 和 0.04）。此外，在女性中，我们发现 ABCA1 DNA 甲基化与高密度脂蛋白胆固醇呈显著负相关（P=0.04），但与其他脂质指标无显著相关性。中介分析显示，在女性中，VC 摄入量通过 ABCA1 DNA 甲基化水平对高密度脂蛋白胆固醇有显著的间接影响（P=0.04）。
尽管本研究不能证明因果关系，但结果表明，ABCA1 DNA 甲基化介导了 VC 对女性高密度脂蛋白胆固醇的保护作用，这为 CVD 预防提供了一个新的生物学机制。
