表观遗传学研究报道了膳食营养素摄入与甲基化水平之间的关系。然而，在这些分析中通常忽略了可能影响DNA甲基化模式的遗传变异，称为甲基化定量位点（mQTL）。我们通过研究估计脂肪酸摄入和ATP结合盒转运蛋白A1（ABCA1）的例子，探讨mQTL是否改变了膳食营养素摄入和白细胞DNAm水平之间的关系。该研究为一横断面研究，共有231名参与者（男性108人，平均年龄为62.7岁），无癌症临床病史，无血脂异常的处方。我们使用测序法测量了ABCA1基因中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。我们使用TaqMan测定了ABCA1的一个遗传变异位点（rs1800976）。通过使用经验证的食物频率问卷并使用残差方法调整总能量摄入，估计了脂肪酸的摄入量。rs1800976等位基因数量越多，ABCA1的平均DNAm水平降低了5%（CC，40.6%; CG，35.9%; GG，30.6%）。较高的n-3多不饱和脂肪酸摄入量与较低的ABCA1 DNAm水平相关（第1组（参考组）vs. 第4组， β［95% CI］：-2.52［-4.77，-0.28］）。在控制rs180076后，膳食n-3多不饱和脂肪酸摄入量与ABCA1 DNAm水平之间的关联减弱了，但仍显示独立关联（第1组（参考组）vs. 第4组， β［95% CI］：-2.00［-3.84，-0.18］）。mQTL和膳食n-3多不饱和脂肪酸摄入量对DNAm水平的交互作用并不显著。这一结果表明，膳食n-3多不饱和脂肪酸摄入量在调整个体遗传背景后，仍是ABCA1基因中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做出贡献。© 2023 The Author(s)，独家授权给 Springer Nature Limited。

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.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.