Department of Preventive Medical Sciences, Fujita Health University School of Medical Sciences, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Japan.
Institute for Biomedicine (affiliated to the University of Lübeck), Eurac Research, Via Alessandro Volta 21, Bolzano/Bozen, Italy.
Eur J Clin Nutr. 2023 Sep;77(9):881-887. doi: 10.1038/s41430-023-01315-6. Epub 2023 Aug 4.
Epigenetic studies have reported relationships between dietary nutrient intake and methylation levels. However, genetic variants that may affect DNA methylation (DNAm) pattern, called methylation quantitative loci (mQTL), are usually overlooked in these analyses. We investigated whether mQTL change the relationship between dietary nutrient intake and leukocyte DNAm levels with an example of estimated fatty acid intake and ATP-binding cassette transporter A1 (ABCA1).
A cross-sectional study on 231 participants (108 men, mean age: 62.7 y) without clinical history of cancer and no prescriptions for dyslipidemia. We measured leukocyte DNAm levels of 8 CpG sites within ABCA1 gene by pyrosequencing method and used mean methylation levels for statistical analysis. TaqMan assay was used for genotyping a genetic variant of ABCA1 (rs1800976). Dietary fatty acid intake was estimated with a validated food frequency questionnaire and adjusted for total energy intake by using residual methods.
Mean ABCA1 DNAm levels were 5% lower with the number of minor alleles in rs1800976 (CC, 40.6%; CG, 35.9%; GG, 30.6%). Higher dietary n-3 PUFA intake was associated with lower ABCA1 DNAm levels (1st (ref) vs. 4th, β [95% CI]: -2.52 [-4.77, -0.28]). After controlling for rs180076, the association between dietary n-3 PUFA intake and ABCA1 DNAm levels was attenuated, but still showed an independent association (1st (ref) vs. 4th, β [95% CI]: -2.00 [-3.84, -0.18]). The interaction of mQTL and dietary n-3 PUFA intake on DNAm levels was not significant.
This result suggested that dietary n-3 PUFA intake would be an independent predictor of DNAm levels in ABCA1 gene after adjusting for individual genetic background. Considering mQTL need to broaden into other genes and nutrients for deeper understanding of DNA methylation, which can contribute to personalized nutritional intervention.
表观遗传学研究已经报告了饮食营养素摄入与甲基化水平之间的关系。然而，这些分析通常忽略了可能影响 DNA 甲基化（DNAm）模式的遗传变异，即称为甲基化定量基因座（mQTL）。我们以脂肪酸摄入和三磷酸腺苷结合盒转运蛋白 A1（ABCA1）为例，研究了 mQTL 是否改变了饮食营养素摄入与白细胞 DNAm 水平之间的关系。
这是一项在 231 名无癌症临床病史且无血脂异常处方的参与者（男性 108 名，平均年龄 62.7 岁）中进行的横断面研究。我们通过焦磷酸测序法测量了 ABCA1 基因内 8 个 CpG 位点的白细胞 DNAm 水平，并使用平均甲基化水平进行统计分析。TaqMan 检测法用于检测 ABCA1 基因的一个遗传变异（rs1800976）。饮食脂肪酸摄入量通过经过验证的食物频率问卷进行估计，并通过残差法调整总能量摄入进行调整。
rs1800976 中的等位基因数量较少（CC 为 40.6%，CG 为 35.9%，GG 为 30.6%），ABCA1 DNAm 水平平均降低 5%。较高的膳食 n-3PUFA 摄入量与较低的 ABCA1 DNAm 水平相关（第 1 （参考）与第 4 组，β[95%CI]：-2.52[-4.77，-0.28]）。在控制 rs180076 后，膳食 n-3PUFA 摄入量与 ABCA1 DNAm 水平之间的关联减弱，但仍呈独立关联（第 1 （参考）与第 4 组，β[95%CI]：-2.00[-3.84，-0.18]）。mQTL 与膳食 n-3PUFA 摄入量对 DNAm 水平的交互作用不显著。
该结果表明，在调整个体遗传背景后，膳食 n-3PUFA 摄入量可能成为 ABCA1 基因 DNAm 水平的独立预测因子。考虑到 mQTL 需要扩展到其他基因和营养素，以更深入地了解 DNA 甲基化，这可以为个性化营养干预提供依据。
