背景:饮食中摄入n-3多不饱和脂肪酸(PUFA)可能对心血管疾病的发展具有保护作用,糖尿病,抑郁症和癌症,而据报道,高摄入n-6PUFA通常与炎症相关性状有关。PUFA对健康结果的影响可能由DNA甲基化(DNAm)介导。我们研究的目的是在奥格斯堡地区的合作健康研究(KORA)FF4队列和莱顿长寿研究(LLS)中确定PUFA摄入对DNAm的影响。
结果:在基于人群的KORAFF4研究(N=1354)和LLS(N=448)的全血中测量DNA甲基化水平,使用IlluminaMethylationitionEPICBeadChip和IlluminaHumanMetrylation450阵列,分别。我们评估了DNAm与KORA和LLS中8种和4种PUFA摄入量之间的关联,分别。在可能的情况下,结果进行荟萃分析。低于Bonferroni校正阈值(p<7.17×10-8),在KORA研究中,我们确定了与PUFA摄入相关的两个差异甲基化位置(DMPs).在模型1中,DMPcg19937480与二十二碳六烯酸(DHA)呈正相关(β:2.00×10-5,95CI:1.28×10-5-2.73×10-5,P值:6.98×10-8),而在我们的完全调整模型中,标记为MARK2基因的cg05041783与二十二碳五烯酸(DPA)呈正相关(β:9.80×10-5,95CI:6.25×10-5-1.33×10-4,P值:6.75×10-8)。在荟萃分析中,我们确定了CpG位点(cg15951061),注释为低于Bonferroni校正(1.23×10-7)的基因CDCA7L,与模型1中二十碳五烯酸(EPA)的摄入量相关(β:2.00×10-5,95%CI:1.27×10-5-2.73×10-5,P值=5.99×10-8),我们分别确认了模型1和2中cg19937480-10×10-91-5-5
结论:我们的研究确定了三个与PUFA摄入相关的CpG位点。这些网站的机制在很大程度上仍未被探索,强调我们发现的新颖性。进一步的研究对于理解CpG位点甲基化与PUFA结果之间的联系至关重要。
Dietary intake of n-3 polyunsaturated fatty acids (PUFA) may have a protective effect on the development of cardiovascular diseases, diabetes, depression and cancer, while a high intake of n-6 PUFA was often reported to be associated with inflammation-related traits. The effect of PUFAs on health outcomes might be mediated by DNA methylation (DNAm). The aim of our
study is to identify the impact of PUFA intake on DNAm in the Cooperative Health Research in the Region of Augsburg (KORA) FF4 cohort and the Leiden Longevity
Study (LLS).
DNA methylation levels were measured in whole blood from the population-based KORA FF4
study (N = 1354) and LLS (N = 448), using the Illumina MethylationEPIC BeadChip and Illumina HumanMethylation450 array, respectively. We assessed associations between DNAm and intake of eight and four PUFAs in KORA and LLS, respectively. Where possible, results were meta-analyzed. Below the Bonferroni correction threshold (p < 7.17 × 10-8), we identified two differentially methylated positions (DMPs) associated with PUFA intake in the KORA
study. The DMP cg19937480, annotated to gene PRDX1, was positively associated with docosahexaenoic acid (DHA) in model 1 (beta: 2.00 × 10-5, 95%CI: 1.28 × 10-5-2.73 × 10-5, P value: 6.98 × 10-8), while cg05041783, annotated to gene MARK2, was positively associated with docosapentaenoic acid (DPA) in our fully adjusted model (beta: 9.80 × 10-5, 95%CI: 6.25 × 10-5-1.33 × 10-4, P value: 6.75 × 10-8). In the meta-analysis, we identified the CpG site (cg15951061), annotated to gene CDCA7L below Bonferroni correction (1.23 × 10-7) associated with eicosapentaenoic acid (EPA) intake in model 1 (beta: 2.00 × 10-5, 95% CI: 1.27 × 10-5-2.73 × 10-5, P value = 5.99 × 10-8) and we confirmed the association of cg19937480 with DHA in both models 1 and 2 (beta: 2.07 × 10-5, 95% CI: 1.31 × 10-5-2.83 × 10-5, P value = 1.00 × 10-7 and beta: 2.19 × 10-5, 95% CI: 1.41 × 10-5-2.97 × 10-5, P value = 5.91 × 10-8 respectively).
Our
study identified three CpG sites associated with PUFA intake. The mechanisms of these sites remain largely unexplored, highlighting the novelty of our findings. Further research is essential to understand the links between CpG site methylation and PUFA outcomes.