FADS1-FADS2 genetic polymorphisms are associated with fatty acid metabolism through changes in DNA methylation and gene expression.
FADS1-FADS2 genetic polymorphisms are associated with fatty acid metabolism through changes in DNA methylation and gene expression.
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FADS1-FADS2 遗传多态性通过 DNA 甲基化和基因表达的变化与脂肪酸代谢相关
DOI：
10.1186/s13148-018-0545-5
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发表时间：
2018-08-29
影响因子：
5.7
通讯作者：
Hu C
中科院分区：
文献类型：
--
作者：
He Z;Zhang R;Jiang F;Zhang H;Zhao A;Xu B;Jin L;Wang T;Jia W;Jia W;Hu C
背景：全基因组关联研究（GWAS）表明，遗传变异是游离脂肪酸水平的重要决定因素。遗传变异和游离脂肪酸水平之间的关联机制尚未完全了解。在这里，我们的目的是确定遗传标记，可以影响不同的脂肪酸水平在中国人口和揭示的DNA甲基化和基因expression.Results的分子机制：我们确定的单核苷酸多态性（SNPs）在脂肪酸去饱和酶（FADS）区域和多个多不饱和脂肪酸之间的强关联。rs174570在FADS 1和FADS 2 mRNA水平上的表达数量性状位点（eQTL）分析表明，rs174570的次要等位基因与FADS 1和FADS 2表达水平的降低相关（P <0. 05）。对FADS区三个选定区域rs174570的DNA甲基化水平进行甲基化数量性状基因座（mQTL）分析显示，FADS 1中4个CpG位点、基因内区域1个CpG位点和FADS 2中3个CpG位点的甲基化水平与rs174570强相关（P < 0.05）。然后，我们证明了FADS 1中三个CpG位点的甲基化水平与FADS 1和FADS 2表达呈负相关，而FADS 2中两个CpG位点与FADS 1和FADS 2表达呈正相关。使用调解分析，我们进一步表明，观察到的rs174570对基因表达的影响是密切相关的预测通过关联与methylation.Conclusions的效果：我们的研究结果表明，在FADS区域的遗传变异是主要的遗传修饰剂，可以通过表观遗传基因调控调节脂肪酸代谢。
Background:Genome-wide association studies (GWASs) have shown that genetic variants are important determinants of free fatty acid levels. The mechanisms underlying the associations between genetic variants and free fatty acid levels are incompletely understood. Here, we aimed to identify genetic markers that could influence diverse fatty acid levels in a Chinese population and uncover the molecular mechanisms in terms of DNA methylation and gene expression.Results:We identified strong associations between single-nucleotide polymorphisms (SNPs) in the fatty acid desaturase (FADS) region and multiple polyunsaturated fatty acids. Expression quantitative trait locus (eQTL) analysis of rs174570 on FADS1 and FADS2 mRNA levels proved that minor allele of rs174570 was associated with decreased FADS1 and FADS2 expression levels (P < 0.05). Methylation quantitative trait locus (mQTL) analysis of rs174570 on DNA methylation levels in three selected regions of FADS region showed that the methylation levels at four CpG sites in FADS1, one CpG site in intragenic region, and three CpG sites in FADS2 were strongly associated with rs174570 (P < 0.05). Then, we demonstrated that methylation levels at three CpG sites in FADS1 were negatively associated with FADS1 and FADS2 expression, while two CpG sites in FADS2 were positively associated with FADS1 and FADS2 expression. Using mediation analysis, we further show that the observed effect of rs174570 on gene expression was tightly correlated with the effect predicted through association with methylation.Conclusions:Our findings suggest that genetic variants in the FADS region are major genetic modifiers that can regulate fatty acid metabolism through epigenetic gene regulation.
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在肾脏疾病的男性和女性中补充N-3长链多不饱和脂肪酸或橄榄油会引起外周血单核细胞中FADS2和ElOVL5的DNA甲基化的差异变化。
影响因子：
3.7
作者：
Hoile SP;Clarke-Harris R;Huang RC;Calder PC;Mori TA;Beilin LJ;Lillycrop KA;Burdge GC
通讯作者：
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作者：
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影响因子：
3.1
作者：
Liu, Fangyuan;Di, Jianzhong;Jia, Weiping
通讯作者：
Jia, Weiping
影响因子：
37.8
作者：
Farvid MS;Ding M;Pan A;Sun Q;Chiuve SE;Steffen LM;Willett WC;Hu FB
通讯作者：
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DOI：
10.1073/pnas.0500398102
发表时间：
2005-07-26
影响因子：
11.1
作者：
Fraga, MF;Ballestar, E;Esteller, M
通讯作者：
Esteller, M