TY - JOUR
T1 - Lipid changes due to fenofibrate treatment are not associated with changes in DNA methylation patterns in the GOLDN study
AU - Das, Mithun
AU - Irvin, M. Ryan
AU - Sha, Jin
AU - Aslibekyan, Stella
AU - Hidalgo, Bertha
AU - Perry, Rodney T.
AU - Zhi, Degui
AU - Tiwari, Hemant K.
AU - Absher, Devin
AU - Ordovas, Jose M.
AU - Arnett, Donna K.
N1 - Publisher Copyright:
� 2015 Das, Irvin, Sha, Aslibekyan, Hidalgo, Perry, Zhi, Tiwari, Absher, Ordovas and Arnett.
PY - 2015
Y1 - 2015
N2 - 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-a, 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.
AB - 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-a, 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.
KW - Cardiovascular disease
KW - DNA methylation
KW - Dyslipidemia
KW - Epigenetic changes
KW - Fenofibrate
KW - Lipid lowering drug
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UR - http://www.scopus.com/inward/citedby.url?scp=84944721667&partnerID=8YFLogxK
U2 - 10.3389/fgene.2015.00304
DO - 10.3389/fgene.2015.00304
M3 - Article
AN - SCOPUS:84944721667
SN - 1664-8021
VL - 6
JO - Frontiers in Genetics
JF - Frontiers in Genetics
IS - SEP
M1 - 304
ER -
