Abstract
BackgroundIdentification of interactions between epigenetic factors and treatments might lead to personalized intervention of diseases. This paper aims to examine the modification effect of fenofibrate therapy on the association of methylation levels and fasting blood triglycerides (TG), and the related biological pathways among methylation sites.ResultsMixed-effects models were employed to assess pre- and posttreatment associations and drug modification effects simultaneously. Five cytosine-phosphate-guanine (CpG) sites were found to be associated with TG levels before and after the fenofibrate therapy: cg00574958, cg17058475, and cg01082498 on CPT1A gene, chromosome 11; cg03725309 on SARS, chromosome 1; and cg06500161 on ABCG1, chromosome 21. In addition, fenofibrate therapy modified the methylation levels on the following 4 CpG sites: cg20015535 (gene EGLN1, chromosome 1); cg24870738 (gene RNF220, chromosome 1); cg06891775 (gene LOC283050, chromosome 10); and cg00607630 (gene USP7, chromosome 16). Further, gene set enrichment analysis (GSEA) identified cancer- and metabolism-related pathways that were associated with TG-related CpG sites.ConclusionsWe identified modification effects of fenofibrate on the associations between blood TG levels and several CpG sites. Pathway enrichment analysis indicated the alternations in some metabolism and cancer-related pathways. Our findings have important implications for future research in pharmacoepigenetics and personalized medicine.
Highlights
Identification of interactions between epigenetic factors and treatments might lead to personalized intervention of diseases
Large-scale genome-wide association studies (GWAS) have identified numerous loci associated with fasting blood lipids and other cardiovascular diseases (CVDs) [1]
The methylation levels of 2 sites on chromosome 11 are associated with pretreatment log TG but not with posttreatment log TG levels
Summary
Identification of interactions between epigenetic factors and treatments might lead to personalized intervention of diseases. This paper aims to examine the modification effect of fenofibrate therapy on the association of methylation levels and fasting blood triglycerides (TG), and the related biological pathways among methylation sites. Large-scale genome-wide association studies (GWAS) have identified numerous loci associated with fasting blood lipids and other cardiovascular diseases (CVDs) [1]. Epigenetic analysis has gained attention in the past few years as an alternative perspective on the etiology of complex diseases. Epigenetic adaptations alter gene expressions and are heritable through many cell divisions, even across generations, while they do not alter the primary DNA sequence. Wei and Wu BMC Genetics 2018, 19(Suppl 1):
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