Allele-specific methylation in the FADS genomic region in DNA from human saliva, CD4+ cells, and total leukocytes.
Allele-specific methylation in the FADS genomic region in DNA from human saliva, CD4+ cells, and total leukocytes.
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DOI：
10.1186/s13148-018-0480-5
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发表时间：
2018
影响因子：
5.7
通讯作者：
Chilton FH
中科院分区：
文献类型：
--
作者：
Rahbar E;Waits CMK;Kirby EH Jr;Miller LR;Ainsworth HC;Cui T;Sergeant S;Howard TD;Langefeld CD;Chilton FH
脂肪酸去饱和酶（FADS）基因簇（人类Chr11）中的遗传变异是肝脏中长链（LC）多不饱和脂肪酸（PUFA）生物合成的重要调节因子，因此与循环LC-PUFA水平相关。最近，表观遗传修饰，如DNA甲基化，特别是在FADS集群中，已被证明会影响LC-PUFA水平。我们的实验室先前证明了等位基因特异性甲基化（ASM）在人肝组织FADS区域的单核苷酸多态性（SNP） rs174537和CpG位点之间的强烈关联。鉴于表观遗传特征具有组织特异性，我们旨在评估rs174537与人唾液、CD4+细胞和来自全血的总白细胞DNA甲基化之间的甲基化状态和ASM相关性。目的是：(1)确定这些外周样本的DNA甲基化是否会显示出与先前在人类肝组织中观察到的类似的ASM趋势；(2)评估DNA甲基化与循环LC-PUFAs之间的关系。在健康志愿者的两个高加索队列中测定了跨越FADS1和FADS2启动子区域以及一个假定的FADS增强子区域的六个CpG位点的DNA甲基化：队列1的白细胞（n = 89，中位年龄= 43，男性占35%）和队列2的唾液和CD4+细胞（n = 32，中位年龄= 41，男性占41%）。在白细胞中观察到rs174537与FADS2启动子区域的三个CpG位点（即chr11:61594865， chr11:61594876, chr11:61594907）和假设增强子区域的一个CpG位点（chr11:61587979）的DNA甲基化之间存在显著的ASM。在CD4+细胞中，在CpG位点chr11:61594876和chr11:61584894处观察到明显的ASM。rs174537位点的基因型与来自白细胞的DNA甲基化显著相关。在CD4+细胞中观察到类似的趋势，但在唾液中没有。来自白细胞和CD4+细胞的DNA甲基化也与循环omega-6 LC-PUFAs显著相关。我们观察到rs174537与白细胞和CD4+细胞FADS区关键调控区域DNA甲基化之间存在显著的ASM。来自白细胞的DNA甲基化也与循环中的omega-6 LC-PUFAs相关。这些结果支持外周全血样本的使用，白细胞在未来的营养基因组学研究中显示出最有希望评估影响人类LC-PUFA生物合成的表观遗传修饰。本文的在线版本（10.1186/s13148-018-0480-5）包含补充材料，授权用户可使用。
Genetic variants within the fatty acid desaturase (FADS) gene cluster (human Chr11) are important regulators of long-chain (LC) polyunsaturated fatty acid (PUFA) biosynthesis in the liver and consequently have been associated with circulating LC-PUFA levels. More recently, epigenetic modifications such as DNA methylation, particularly within the FADS cluster, have been shown to affect LC-PUFA levels. Our lab previously demonstrated strong associations of allele-specific methylation (ASM) between a single nucleotide polymorphism (SNP) rs174537 and CpG sites across the FADS region in human liver tissues. Given that epigenetic signatures are tissue-specific, we aimed to evaluate the methylation status and ASM associations between rs174537 and DNA methylation obtained from human saliva, CD4+ cells and total leukocytes derived from whole blood. The goals were to (1) determine if DNA methylation from these peripheral samples would display similar ASM trends as previously observed in human liver tissues and (2) evaluate the associations between DNA methylation and circulating LC-PUFAs. DNA methylation at six CpG sites spanning FADS1 and FADS2 promoter regions and a putative FADS enhancer region were determined in two Caucasian cohorts of healthy volunteers: leukocytes in cohort 1 (n = 89, median age = 43, 35% male) and saliva and CD4+ cells in cohort 2 (n = 32, median age = 41, 41% male). Significant ASM between rs174537 and DNA methylation at three CpG sites located in the FADS2 promoter region (i.e., chr11:61594865, chr11:61594876, chr11:61594907) and one CpG site in the putative enhancer region (chr11:61587979) were observed with leukocytes. In CD4+ cells, significant ASM was observed at CpG sites chr11:61594876 and chr11:61584894. Genotype at rs174537 was significantly associated with DNA methylation from leukocytes. Similar trends were observed with CD4+ cells, but not with saliva. DNA methylation from leukocytes and CD4+ cells also significantly correlated with circulating omega-6 LC-PUFAs. We observed significant ASM between rs174537 and DNA methylation at key regulatory regions in the FADS region from leukocyte and CD4+ cells. DNA methylation from leukocytes also correlated with circulating omega-6 LC-PUFAs. These results support the use of peripheral whole blood samples, with leukocytes showing the most promise for future nutrigenomic studies evaluating epigenetic modifications affecting LC-PUFA biosynthesis in humans. The online version of this article (10.1186/s13148-018-0480-5) contains supplementary material, which is available to authorized users.
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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：
Burdge GC
影响因子：
4.6
作者：
de la Rocha C;Pérez-Mojica JE;León SZ;Cervantes-Paz B;Tristán-Flores FE;Rodríguez-Ríos D;Molina-Torres J;Ramírez-Chávez E;Alvarado-Caudillo Y;Carmona FJ;Esteller M;Hernández-Rivas R;Wrobel K;Wrobel K;Zaina S;Lund G
通讯作者：
Lund G
影响因子：
5.3
作者：
Kwak, Jung Hyun;Paik, Jean Kyung;Lee, Jong Ho
通讯作者：
Lee, Jong Ho
影响因子：
3.7
作者：
Rahbar E;Ainsworth HC;Howard TD;Hawkins GA;Ruczinski I;Mathias R;Seeds MC;Sergeant S;Hixson JE;Herrington DM;Langefeld CD;Chilton FH
通讯作者：
Chilton FH
DOI：
10.1016/j.jnutbio.2012.09.005
发表时间：
2013-07
期刊：
The Journal of nutritional biochemistry
影响因子：
--
作者：
Hoile SP;Irvine NA;Kelsall CJ;Sibbons C;Feunteun A;Collister A;Torrens C;Calder PC;Hanson MA;Lillycrop KA;Burdge GC
通讯作者：
Burdge GC