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

• Published in: PloS one Vol. 11; no. 1; p. e0145789
• Main Authors: Das, Mithun, Sha, Jin, Hidalgo, Bertha, Aslibekyan, Stella, Do, Anh N., Zhi, Degui, Sun, Dianjianyi, Zhang, Tao, Li, Shengxu, Chen, Wei, Srinivasan, Sathanur R., Tiwari, Hemant K., Absher, Devin, Ordovas, Jose M., Berenson, Gerald S., Arnett, Donna K., Irvin, Marguerite R.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.01.2016; Public Library of Science (PLoS)
• Subjects: Aged; Anthropometry; Automation; Biology and life sciences; Black or African American; Black People - genetics; Blood Pressure; Carnitine O-Palmitoyltransferase - genetics; Carnitine O-Palmitoyltransferase - physiology; CD4 antigen; Chromosome 11; Chromosomes, Human, Pair 11 - genetics; Cohort Studies; CpG islands; CpG Islands - genetics; Cytosine; Deoxyribonucleic acid; Diet; DNA; DNA Methylation; Drugs; Epigenetics; Female; Genetics; Guanine; Humans; Lymphocytes; Lymphocytes T; Male; Medicine and Health Sciences; Metabolic disorders; Metabolic syndrome; Metabolic Syndrome - ethnology; Metabolic Syndrome - genetics; Middle Aged; Minnesota - epidemiology; Nutrition research; Oligonucleotide Array Sequence Analysis; People and places; Phosphates; Risk Factors; Triglycerides - blood; Utah - epidemiology; White People - genetics; Minnesota; Utah
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0145789

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.