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

• DOI: 10.1371/journal.pone.0145789
• Publication Date: 2016-01-25T19:19:04Z
• Authors: Mithun Das; Jin Sha; Bertha Hidalgo; Stella Aslibekyan; Anh N. Do; Degui Zhi; Dianjianyi Sun; Tao Zhang; Shengxu Li; Wei Chen; Sathanur R. Srini...; Hemant K. Tiwari; Devin Absher; Jose M. Ordovas; Gerald S. Berenson; Donna K. Arnett; Marguerite R. Irvin
• Keywords: Male; 0301 basic medicine; Science; Minnesota; Black People; Blood Pressure; White People; Cohort Studies; 03 medical and health sciences; Risk Factors; Utah; Humans; Triglycerides; Aged; Oligonucleotide Array Sequence Analysis; Metabolic Syndrome; Anthropometry; Carnitine O-Palmitoyltransferase; Chromosomes, Human, Pair 11; Q; R; DNA Methylation; Middle Aged; Medicine; CpG Islands; Female; Research Article

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.