|DAS, MITHUN - University Of Alabama|
|SHA, JIN - University Of Alabama|
|HIDALGO, BERTHA - University Of Alabama|
|ASLIBEKYAN, STELLA - University Of Alabama|
|DO, ANH - University Of Alabama|
|ZHI, DEGUI - University Of Alabama|
|SUN, DIANJIANYI - Tulane University|
|ZHANG, TAO - Tulane University|
|LI, SHENGXU - Tulane University|
|CHEN, WEI - Tulane University|
|SRINIVASAN, SATHANUR - Tulane University|
|TIWARI, HEMANT - University Of Alabama|
|ABSHER, DEVIN - Hudsonalpha Institute For Biotechnology|
|ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|BERENSON, GERALD - Tulane University|
|ARNETT, DONNA - University Of Kentucky|
|IRVIN, MARGUERITE - University Of Alabama|
Submitted to: PLoS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/8/2015
Publication Date: 1/25/2016
Citation: Das, M., Sha, J., Hidalgo, B., Aslibekyan, S., Do, A.N., Zhi, D., Sun, D., Zhang, T., Li, S., Chen, W., Srinivasan, S., Tiwari, H.K., Absher, D.M., Ordovas, J.M., Berenson, G.S., Arnett, D.K., Irvin, M.R. 2016. Association of DNA methylation at CPT1A locus with metabolic syndrome in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study. PLoS One. 11(1):e0145789. https://doi.org/10.1371/journal.pone.0145789.
Interpretive Summary: Metabolic syndrome is a clustering of medical conditions (i.e., abdominal obesity, high blood pressure, high blood sugar, elevated serum triglycerides and low high-density lipoprotein (HDL) levels,) and it is associated with the risk of developing cardiovascular disease and type 2 diabetes. In the US, about a quarter of the adult population has metabolic syndrome, and the prevalence increases with age, with racial and ethnic minorities being particularly affected. The risk of metabolic syndrome is defined by the interaction of genetic and environmental factors and epigenetics. More specifically, methylation is the bridge by which the environment communicates with the genome to regulate gene expression. To improve our understanding of the methylation sites in the genome associated with the metabolic syndrome, we conducted a whole genome investigation using DNA isolated from 846 participants in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). Our results show that two methylation sites in the CPT1A gene were significantly associated with metabolic syndrome. These findings were replicated in both European and African ancestry participants of the Bogalusa Heart Study. Our results suggest that methylation in CPT1A is a promising epigenetic marker for metabolic syndrome risk and could become useful as a treatment target in the future.
Technical 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.