Epigenetic Determinants of Lipid Response to Dietary Fat and Fenofibrate
膳食脂肪和非诺贝特脂质反应的表观遗传决定因素
基本信息
- 批准号:9250286
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-06-30 至 2018-05-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Dyslipidemias play a large role in the occurrence of cardiovascular disease, which has fueled
interest to better understand environmental factors responsible for dyslipidemias, especially
hypertriglyceridemia. Epigenetic variations may affect triglyceride (TG) metabolism and
response to environmental challenges. Our goal is to conduct the first experiments that will
comprehensively scan the epigenome for determinants of TG and other dyslipidemic responses
to two “environmental” interventions, one to raise TGs (a high-fat meal), and one to lower TGs
(3-week fenofibrate treatment). These experiments will be conducted in the NHLBI Program in
Gene-Environment Interaction Network's “Genetics of Lipid Lowering and Diet” (GOLDN) study.
GOLDN recruited family members from field centers in Minnesota and Utah and phenotyped
them extensively for enzymatic and NMR lipids and inflammatory markers in response to the
two interventions. The proposed study will build upon this unique resource using previously
collected samples to implement the following aims: (1) Conduct genome-wide CpG methylation
analysis, using next generation sequencing method, specifically, Reduced Representation
Bisulfite Sequencing, in 1,048 individuals from 184 families to identify epigenetic variation
contributing to the response of TGs and TG-related phenotypes to a fat meal, fenofibrate, and a
fat meal in the context of fenofibrate treatment. From these results, we will select 20 candidate
genes with the best evidence for further characterization in Aim 2. (2) Characterize the
methylation state of these 20 genes using bisulfite sequencing of promoters and other regions
of interest in all 1,048 family members. (3) Replicate significant findings from Aims 1 and 2 in
external cohorts. (4) Conduct gene expression studies to identify the functional impact of
methylation findings from Aims 1-3 since DNA methylation may affect the expression of nearby
genes in a variety of ways, including transcription rates, alternative splicing, microRNA
inhibition, or allele specific expression. We will apply next-generation sequencing to both
mRNA and microRNA from 150 subjects using a method called RNAseq. If successful, we will
identify novel epigenetic variations that predict individuals who respond poorly to dietary fat or
favorably to fenofibrate which will lead to the development of targeted interventions to more
effectively prevent and treat hypertriglyceridemia.
血脂异常在心血管疾病的发生中起着重要作用,
有兴趣更好地了解负责血脂异常的环境因素,特别是
高胆固醇血症表观遗传变异可能影响甘油三酯(TG)代谢,
应对环境挑战。我们的目标是进行第一次实验,
全面扫描表观基因组,寻找TG和其他血脂异常反应的决定因素
两种“环境”干预,一种是提高TG(高脂肪餐),另一种是降低TG
(3周非诺贝特治疗)。这些实验将在NHLBI计划中进行,
基因-环境相互作用网络的“降脂和饮食的遗传学”(GOLDN)研究。
GOLDN从明尼苏达州和犹他州的野外中心招募了家庭成员,
他们广泛用于酶和NMR脂质和炎症标志物,以响应
两次发言。拟议的研究将利用这一独特的资源,
收集样本以实现以下目的:(1)进行全基因组CpG甲基化
分析,使用下一代测序方法,特别是简化表示法
亚硫酸氢盐测序,来自184个家庭的1,048名个体,以确定表观遗传变异
促进TG和TG相关表型对脂肪餐、非诺贝特和
脂肪餐在非诺贝特治疗的背景下。从这些结果中,我们将选出20名候选人,
目的2中具有进一步表征的最佳证据的基因。(2)表征
使用启动子和其它区域的亚硫酸氢盐测序来检测这20个基因的甲基化状态
所有1,048名家庭成员(3)将目标1和2的重要结果复制到
外部队列。(4)进行基因表达研究,以确定
目的1 - 3的甲基化发现,因为DNA甲基化可能影响附近的
基因以各种方式,包括转录率,选择性剪接,microRNA
抑制或等位基因特异性表达。我们将把下一代测序技术应用于
使用称为RNAseq的方法从150名受试者中提取mRNA和microRNA。如果成功,我们将
识别新的表观遗传变异,预测对膳食脂肪反应不良的个体,
有利的非诺贝特,这将导致有针对性的干预措施的发展,
有效预防和治疗高血脂症。
项目成果
期刊论文数量(6)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Genome- and CD4+ T-cell methylome-wide association study of circulating trimethylamine-N-oxide in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN).
- DOI:10.1016/j.jnim.2017.03.002
- 发表时间:2017-06-01
- 期刊:
- 影响因子:0
- 作者:Aslibekyan, Stella;Irvin, Marguerite R;Arnett, Donna K
- 通讯作者:Arnett, Donna K
CPT1A: the future of heart disease detection and personalized medicine?
- DOI:10.2217/clp.13.75
- 发表时间:2014
- 期刊:
- 影响因子:0
- 作者:Irvin MR;Aslibekyan S;Hidalgo B;Arnett D
- 通讯作者:Arnett D
Hypermethylation of MIR21 in CD4+ T cells from patients with relapsing-remitting multiple sclerosis associates with lower miRNA-21 levels and concomitant up-regulation of its target genes.
- DOI:10.1177/1352458517721356
- 发表时间:2018-09
- 期刊:
- 影响因子:0
- 作者:Ruhrmann S;Ewing E;Piket E;Kular L;Cetrulo Lorenzi JC;Fernandes SJ;Morikawa H;Aeinehband S;Sayols-Baixeras S;Aslibekyan S;Absher DM;Arnett DK;Tegner J;Gomez-Cabrero D;Piehl F;Jagodic M
- 通讯作者:Jagodic M
Clinical applications of epigenetics in cardiovascular disease: the long road ahead.
- DOI:10.1016/j.trsl.2014.04.004
- 发表时间:2015-01
- 期刊:
- 影响因子:0
- 作者:Aslibekyan S;Claas SA;Arnett DK
- 通讯作者:Arnett DK
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Donna K Arnett其他文献
1030-139 Prevalence and correlates of mitral regurgitation in hypertensive patients: The hypergen study
- DOI:
10.1016/s0735-1097(04)91806-2 - 发表时间:
2004-03-03 - 期刊:
- 影响因子:
- 作者:
Zhi Bin Li;Richard B Devereux;Jennifer E Liu;Dalane W Kitzman;Albert Oberman;Paul N Hopkins;Charles C Gu;Donna K Arnett - 通讯作者:
Donna K Arnett
1142-179 Body fat distribution influences cardiac output in normotensive and hypertensive overweight individuals: The hyperGEN study
- DOI:
10.1016/s0735-1097(04)92168-7 - 发表时间:
2004-03-03 - 期刊:
- 影响因子:
- 作者:
Giovanni de Simone;Richard B Devereux;Marcello Chinali;Vittorio Palmieri;Albert Oberman;Dalane W Kitzman;Paul N Hopkins;D.C Rao;Donna K Arnett - 通讯作者:
Donna K Arnett
Donna K Arnett的其他文献
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{{ truncateString('Donna K Arnett', 18)}}的其他基金
Genetic and Molecular Markers of Methotrexate Efficacy and Toxicity in Early...
早期甲氨蝶呤功效和毒性的遗传和分子标记...
- 批准号:
8304146 - 财政年份:2011
- 资助金额:
-- - 项目类别:
Epigenetic Determinants of Lipid Response to Dietary Fat and Fenofibrate
膳食脂肪和非诺贝特脂质反应的表观遗传决定因素
- 批准号:
8300134 - 财政年份:2010
- 资助金额:
-- - 项目类别:
Epigenetic Determinants of Lipid Response to Dietary Fat and Fenofibrate
膳食脂肪和非诺贝特脂质反应的表观遗传决定因素
- 批准号:
8509004 - 财政年份:2010
- 资助金额:
-- - 项目类别:
Epigenetic Determinants of Lipid Response to Dietary Fat and Fenofibrate
膳食脂肪和非诺贝特脂质反应的表观遗传决定因素
- 批准号:
8130808 - 财政年份:2010
- 资助金额:
-- - 项目类别:
Epigenetic Determinants of Lipid Response to Dietary Fat and Fenofibrate
膳食脂肪和非诺贝特脂质反应的表观遗传决定因素
- 批准号:
9120549 - 财政年份:2010
- 资助金额:
-- - 项目类别:
Epigenetic Determinants of Lipid Response to Dietary Fat and Fenofibrate
膳食脂肪和非诺贝特脂质反应的表观遗传决定因素
- 批准号:
7949793 - 财政年份:2010
- 资助金额:
-- - 项目类别:
Genomewide Association Study of Lipid Response to Fenofibrate and Dietary Fat
非诺贝特和膳食脂肪的脂质反应的全基因组关联研究
- 批准号:
8129753 - 财政年份:2008
- 资助金额:
-- - 项目类别:
Genomewide Association Study of Lipid Response to Fenofibrate and Dietary Fat
非诺贝特和膳食脂肪的脂质反应的全基因组关联研究
- 批准号:
9316688 - 财政年份:2008
- 资助金额:
-- - 项目类别:
Genomewide Association Study of Lipid Response to Fenofibrate and Dietary Fat
非诺贝特和膳食脂肪的脂质反应的全基因组关联研究
- 批准号:
7682091 - 财政年份:2008
- 资助金额:
-- - 项目类别:
Genetic and Molecular Markers of Methotrexate Efficacy and Toxicity in Early...
早期甲氨蝶呤功效和毒性的遗传和分子标记...
- 批准号:
7475994 - 财政年份:2008
- 资助金额:
-- - 项目类别:
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