Abstract MP56: Epigenome-wide association study of lipid and inflammatory marker to response fenofibrate in the Genetics of Lipid Lowering Drugs and Diet Network Study
Introduction: There is considerable inter-individual variation in response to lipid-lowering drug therapies. This study aimed to discover the epigenetic factors associated with response to fenofibrate, which may be used to facilitate initiatives in personalized medicine.
Methods: We conducted an epigenome-wide association study for lipid and inflammatory marker response to 3 weeks of daily treatment with 160 mg of fenofibrate among 749 participants in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study. For both lipids and inflammatory markers, we analyzed the ratio of the post-3 week lipid or inflammatory marker concentration divided by the baseline concentration. We fit mixed models with methylation status of each CpG as the dependent variable and lipid or inflammatory ratio as the variable of interest adjusting for age, sex, study site, and T-cell purity (fixed effects) and family structure (random effect). A Bonferroni corrected P-value of 1.1x10^-7 was considered significant.
Results: Methylation of a CpG site in CPT1A on chromosome 11 was significantly associated with LDL cholesterol response to fenofibrate (P=4.18x10-8). In addition, a CpG site in NEU2 on chromosome 2, was significantly associated with IL2 response (P=7.80x10-7). CPT1A plays an important role in fatty acid metabolism, whereas NEU2 is a type of salidase known to be involved in the development of atherosclerosis.
Conclusions: Our findings suggest that methylation of CpG sites within CPT1A and NEU2 are associated with LDL cholesterol and IL2 response to fenofibrate, respectively, and could prove useful for identifying patients who benefit from fenofibrate therapy.
Author Disclosures: B. Hidalgo: None. R. Irvin: None. S. Aslibekyan: None. J. Sha: None. D. Zhi: None. D. Absher: None. J. Ordovas: None. H. Tiwari: None. D. Arnett: None.
- © 2014 by American Heart Association, Inc.