Association of DNA Methylation at CPT1A Locus with Metabolic Syndrome in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study.
Association of DNA Methylation at CPT1A Locus with Metabolic Syndrome in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study.
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DOI：
10.1371/journal.pone.0145789
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Irvin MR
中科院分区：
文献类型：
--
作者：
Das M;Sha J;Hidalgo B;Aslibekyan S;Do AN;Zhi D;Sun D;Zhang T;Li S;Chen W;Srinivasan SR;Tiwari HK;Absher D;Ordovas JM;Berenson GS;Arnett DK;Irvin MR
在这项研究中，我们在降脂药物和饮食遗传学网络（GOLDN）的846名欧洲血统参与者中进行了代谢综合征（MetS）的表观基因组关联研究。从CD 4 + T细胞中分离DNA，并使用Illumina Infinium HumanMethylation 450 BeadChip测定约470，000个胞嘧啶-磷酸-鸟嘌呤二核苷酸（CpG）对处的甲基化。我们使用线性混合模型将单个CpG的甲基化百分比建模为MetS的函数。Bonferroni校正后的P值为1.1 x 10−7，则认为具有显著性。11号染色体上CPT 1A中两个CpG位点的甲基化与MetS显著相关（cg 00574958的P = 2.6x10-14，cg 17058475的P = 1.2x10-9）。在博加卢萨心脏研究的欧洲和非洲血统的参与者中重复了显著的相关性。我们的研究结果表明，CPT 1A的甲基化是MetS风险的一个有希望的表观遗传标记，在未来可能成为一个有用的治疗靶点。
In this study, we conducted an epigenome-wide association study of metabolic syndrome (MetS) among 846 participants of European descent in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). DNA was isolated from CD4+ T cells and methylation at ~470,000 cytosine-phosphate-guanine dinucleotide (CpG) pairs was assayed using the Illumina Infinium HumanMethylation450 BeadChip. We modeled the percentage methylation at individual CpGs as a function of MetS using linear mixed models. A Bonferroni-corrected P-value of 1.1 x 10−7 was considered significant. Methylation at two CpG sites in CPT1A on chromosome 11 was significantly associated with MetS (P for cg00574958 = 2.6x10-14 and P for cg17058475 = 1.2x10-9). Significant associations were replicated in both European and African ancestry participants of the Bogalusa Heart Study. Our findings suggest that methylation in CPT1A is a promising epigenetic marker for MetS risk which could become useful as a treatment target in the future.