Skip to main content
ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #319150
Title: Methylation at CPT1A locus is associated with lipoprotein subfraction profiles

Author
item FRAZIER-WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC)
item ASLIBEKYAN, STELLA - Baylor College Of Medicine
item ABSHER, DEVIN - University Of Alabama
item HOPKINS, PAUL - University Of Utah
item JIN, SHA - University Of Alabama
item TSAI, MICHAEL - University Of Minnesota
item TIWARI, HEMANT - University Of Alabama
item WAITE, LINDSAY - University Of Alabama
item ZHI, DEGUI - University Of Alabama
item ARNETT, DONNA - University Of Alabama

Submitted to: Journal of Lipid Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/1/2014
Publication Date: 4/7/2014
Citation: Frazier-Wood, A.C., Aslibekyan, S., Absher, D.M., Hopkins, P.N., Jin, S., Tsai, M.Y., Tiwari, H.K., Waite, L.L., Zhi, D., Arnett, D.K. 2014. Methylation at CPT1A locus is associated with lipoprotein subfraction profiles. Journal of Lipid Research. 7(55):1324-1330.

Interpretive Summary: Lipoproteins are particles that carry cholesterol in the blood to either be destroyed by the body or deposited as a fatty plaque in the arteries. Differences in sizes of the lipoproteins indicate differential risk for depositing cholesterol and plaques and as the plaques are associated with cardiovascular disease, different sizes of lipoproteins indicate different levels of cardiovascular disease risk. We need to understand what causes lipoprotein size differences to know how to treat 'risky' lipoprotein size profiles. We hypothesized that gene expression (as measured by DNA methylation levels, which indicates whether a gene is 'tuned on' or (turned off') contributes to lipoprotein size differences as we know there are genetic causes too. Therefore, we looked across the whole genome and found two loci, both in the carnitine palmitoyltransferase-1A (CPT1A) gene, where DNA methylation levels associate with lipoprotein size. Since DNA methylation can be changed via, for example, exercise or drug intervention this study is important as it gives us a place in the genome to target our interventions to reduce cardiovascular risk.

Technical Abstract: Lipoprotein subfractions help discriminate cardiometabolic disease risk. Genetic loci validated as associating with lipoprotein measures do not account for a large proportion of the individual variation in lipoprotein measures. We hypothesized that DNA methylation levels across the genome contribute to interindividual variation in lipoprotein measures. Using data from participants of the Genetics of Lipid Lowering Drugs and Diet Network (n = 663 for discovery and n = 331 for replication stages, respectively), we conducted the first systematic screen of the genome to determine associations between methylation status at ~470,000 cytosine-guanine dinucleotide (CpG) sites in CD4+ T cells and 14 lipoprotein subfraction measures. We modeled associations between methylation at each CpG site and each lipoprotein measure separately using linear mixed models, adjusted for age, sex, study site, cell purity, and family structure. We identified two CpGs, both in the carnitine palmitoyltransferase-1A (CPT1A) gene, which reached significant levels of association with VLDL and LDL subfraction parameters in both discovery and replication phases (P < 1.1x10-7 in the discovery phase, P <.004 in the replication phase, and P<1.1x10-12 in the full sample). CPT1A is regulated by PPARa, a ligand for drugs used to reduce CVD. Our associations between methylation in CPT1A and lipoprotein measures highlight the epigenetic role of this gene in metabolic dysfunction.