Lipid changes due to fenofibrate treatment are not associated with changes in DNA methylation patterns in the GOLDN study.
Fenofibrate lowers triglycerides (TG) and raises high density lipoprotein cholesterol (HDLc) in dyslipidemic individuals. Several studies have shown genetic variability in lipid responses to fenofibrate treatment. It is, however, not known whether epigenetic patterns are also correlated with the changes in lipids due to fenofibrate treatment. The present study was therefore undertaken to examine the changes in DNA methylation among the participants of Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study. A total of 443 individuals were studied for epigenome-wide changes in DNA methylation, assessed using the Illumina Infinium HumanMethylation450 array, before and after a 3-week daily treatment with 160 mg of fenofibrate. The association between the change in DNA methylation and changes in TG, HDLc, and low-density lipoprotein cholesterol (LDLc) were assessed using linear mixed models adjusted for age, sex, baseline lipids, and study center as fixed effects and family as a random effect. Changes in DNA methylation were not significantly associated with changes in TG, HDLc, or LDLc after 3 weeks of fenofibrate for any CpG. CpG changes in genes known to be involved in fenofibrate response, e.g., PPAR-α, APOA1, LPL, APOA5, APOC3, CETP, and APOB, also did not show evidence of association. In conclusion, changes in lipids in response to 3-week treatment with fenofibrate were not associated with changes in DNA methylation. Studies of longer duration may be required to detect treatment-induced changes in methylation.
Department of Epidemiology, School of Public Health, University of Alabama at Birmingham Birmingham, AL, USA.
Mithun
M
Das
Department of Epidemiology, School of Public Health, University of Alabama at Birmingham Birmingham, AL, USA.
M Ryan
MR
Irvin
Department of Epidemiology, School of Public Health, University of Alabama at Birmingham Birmingham, AL, USA.
Jin
J
Sha
Department of Epidemiology, School of Public Health, University of Alabama at Birmingham Birmingham, AL, USA.
Stella
S
Aslibekyan
Department of Epidemiology, School of Public Health, University of Alabama at Birmingham Birmingham, AL, USA.
Bertha
B
Hidalgo
Department of Epidemiology, School of Public Health, University of Alabama at Birmingham Birmingham, AL, USA.
Rodney T
RT
Perry
Department of Biostatistics, Section on Statistical Genetics, School of Public Health, University of Alabama at Birmingham Birmingham, AL, USA.
Degui
D
Zhi
Department of Biostatistics, Section on Statistical Genetics, School of Public Health, University of Alabama at Birmingham Birmingham, AL, USA.
Hemant K
HK
Tiwari
Absher Laboratory, HudsonAlpha Institute of Biotechnology Huntsville, AL, USA.
Devin
D
Absher
Nutrition and Genomics Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University Boston, MA, USA.
Jose M
JM
Ordovas
Department of Epidemiology, School of Public Health, University of Alabama at Birmingham Birmingham, AL, USA.
Donna K
DK
Arnett
DNA methylation; cardiovascular disease; dyslipidemia; epigenetic changes; fenofibrate; lipid lowering drug