DNA methylation in human lipid metabolism and related diseases

Abstract

Purpose of reviewIt is becoming increasingly evident that epigenetic mechanisms, particularly DNA methylation, play a role in the regulation of blood lipid levels and lipid metabolism-linked phenotypes and diseases.Recent findingsRecent genome-wide methylation and candidate gene studies of blood lipids have highlighted several robustly replicated methylation markers across different ethnicities. Furthermore, many of these lipid-related CpG sites associated with blood lipids are also linked to lipid-related phenotypes and diseases. Integrating epigenome-wide association studies (EWAS) data with other layers of molecular data such as genetics or the transcriptome, accompanied by relevant statistical methods (e.g. Mendelian randomization), provides evidence for causal relationships. Recent data suggest that epigenetic changes can be consequences rather than causes of dyslipidemia. There is sparse information on many lipid classes and disorders of lipid metabolism, and also on the interplay of DNA methylation with other epigenetic layers such as histone modifications and regulatory RNAs.SummaryThe current review provides a literature overview of epigenetic modifications in lipid metabolism and other lipid-related phenotypes and diseases focusing on EWAS of DNA methylation from January 2016 to September 2017. Recent studies strongly support the importance of epigenetic modifications, such as DNA methylation, in lipid metabolism and related diseases for relevant biological insights, reliable biomarkers, and even future therapeutics.

Thioredoxin‐interacting protein promotes activation and inflammation of monocytes with DNA demethylation in coronary artery disease

“…In our study, TC and FPG levels were both significantly relevant to methylation of cg19693031, which was coincident to the previous study . Specifically, studies suggested that DNA methylation could be altered by dyslipidemia and the stimulation of insulin or glucose . For example, insulin could lead to changed DNA methylation in the 3′ UTR of ATP2A3.…”

“…25,26,42,43 Specifically, studies suggested that DNA methylation could be altered by dyslipidemia and the stimulation of insulin or glucose. 44,45 For example, insulin could lead to changed DNA methylation in the 3′ UTR of ATP2A3. Dysregulated lipid metabolism could induce overexpressed TXNIP by promoting endoplasmic reticulum (ER) stress.…”

Distinctive pattern of AHNAK methylation level in peripheral blood mononuclear cells and the association with HBV‐related liver diseases

“…Epigenetic modification is an important mechanism for the occurrence and development of many metabolic diseases and cancers . DNA methylation is recognized as one of the first discovered epigenetic modifications, which can regulate gene expression by influencing chromatin structure, DNA conformation, DNA stability, and DNA‐protein action mode .…”

The role of genetic testing in dyslipidaemia

“…22 Epigenetics is increasingly recognised as affecting genotype-phenotype relationships. Incorporating epigenetic analysis using methylation arrays 23 or other assays into standard genetic practice may be on the horizon. 9 However, for dyslipidaemias this is limited by the fact that epigenetic imprinting in relevant tissues such as liver or intestine is not faithfully reflected by patterns in white blood cells, which are the usual convenient source of genetic material.…”