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Member Research and Reports

Member Research and Reports

UAB Looks for Link between Fenofibrate Treatment and Changes in DNA Methylation Patterns

“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,” says Dr. Donna K. Arnett, professor and chair in the department of epidemiology at the University of Alabama at Birmingham. Therefore, Dr. Arnett led a team — including department colleagues Dr. Ryan Irvin, assistant professor; Mr. Jin Sha, statistician; Dr. Stella Aslibekyan, assistant professor; Dr. Bertha Hidalgo, assistant professor; and Dr. Rodney T. Perry, research assistant professor; as well as Dr. Degui Zhi, assistant professor, and Dr. Hemant K. Tiwari, professor, in the department of biostatistics, section on statistical genetics — to examine the changes in DNA methylation among 443 participants of the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study.

Donna Arnett en las instalaciones del CNIC de Madrid el 13 de mayo de 2013

[Photo: Dr. Donna K. Arnett]

Using the Illumina Infinium HumanMethylation450 array, analysis of the study subjects was performed for epigenome-wide changes in DNA methylation, both before and after a three-week daily treatment with 160 mg of fenofibrate. The researchers observed that “[t]he 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 three 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.”

Findings indicate that changes in lipids in response to three-week treatment with fenofibrate were not linked to changes in DNA methylation. Dr. Arnett and her colleagues noted that longer studies may be required to detect treatment-induced changes in methylation.

“Lipid Changes Due to Fenofibrate Treatment Are Not Associated with Changes in DNA Methylation Patterns in the GOLDN Study” was published in September in the journal Frontiers in Genetics.

Journal article: http://journal.frontiersin.org/article/10.3389/fgene.2015.00304/abstract