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Multicenter Study
. 2016 Jan 25;11(1):e0145789.
doi: 10.1371/journal.pone.0145789. eCollection 2016.

Association of DNA Methylation at CPT1A Locus with Metabolic Syndrome in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study

Mithun Das  1 , Jin Sha  1 , Bertha Hidalgo  1 , Stella Aslibekyan  1 , Anh N Do  1 , Degui Zhi  2 , Dianjianyi Sun  3 , Tao Zhang  3 , Shengxu Li  3 , Wei Chen  3 , Sathanur R Srinivasan  3 , Hemant K Tiwari  2 , Devin Absher  4 , Jose M Ordovas  5   6 , Gerald S Berenson  3 , Donna K Arnett  7 , Marguerite R Irvin  1
Affiliations
Multicenter Study

Association of DNA Methylation at CPT1A Locus with Metabolic Syndrome in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study

Mithun Das et al. PLoS One. .

Abstract

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist. Dr. Absher is affiliated with HudsonAlpha Institute for Biotechnology of Huntsville, Alabama, United States of America, a non-profit institute dedicated to research, education, and enterprise. This affiliation does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Epigenome-wide association Manhattan plot for MetS in the GOLDN dataset (n = 846). MetS; metabolic syndrome.
The blue line indicates a marginal significance level of 1.0 x 10−5; the red line indicates the genome-wide significance level of 1.1 x 10−7.
Fig 2
Fig 2. Differences in mean DNA methylation (%) of cg00574958 in CPT1A by risk factors of MetS.
X-axis shows the criteria met (yes/no) for each component of MetS; Y-axis the mean DNA methylation (%) with error bars showing standard error. *P < 0.01, **P < 0.001. Black bars, MetS criteria not met; gray bars, MetS criteria met. MetS criteria include the following: waist circumference ≥ 102 cm for men and ≥ 88 cm for women; high-density lipoprotein cholesterol < 40 mg/dL for men and < 50 mg/dL for women; triglycerides ≥ 150 mg/dL; blood pressure (systolic/diastolic) ≥ 130 / ≥85 mm Hg; and fasting blood glucose ≥ 100 mg/dL.
See this image and copyright information in PMC

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