DNA Methylation and High-Density Lipoprotein Functionality-Brief Report: The REGICOR Study (Registre Gironi del Cor)

Arterioscler Thromb Vasc Biol. 2017 Mar;37(3):567-569. doi: 10.1161/ATVBAHA.116.308831. Epub 2017 Jan 5.

Abstract

Objective: The function of high-density lipoproteins (HDLs) may better reflect their atheroprotective role, compared with HDL-cholesterol levels. The association between DNA methylation and HDL function has not yet been established.

Approach and results: We designed an epigenome-wide association study including 645 individuals from the REGICOR study (Registre Gironi del Cor). We determined DNA methylation from peripheral blood cells using the HumanMethylation450 array. We analyzed HDL functionality by determining HDL cholesterol efflux capacity and HDL inflammatory index. We discovered 3 methylation sites located in HOXA3, PEX5, and PER3 related to cholesterol efflux capacity and 1 located in GABRR1 related to HDL inflammatory index. Using a candidate gene approach, we also found 2 methylation sites located in CMIP related to cholesterol efflux capacity.

Conclusions: We identified 6 potential loci associated with HDL functionality in HOXA3, PEX5, PER3, CMIP, and GABRR1. Additional studies are warranted to validate these findings in other populations.

Keywords: DNA methylation; atherosclerosis; blood cells; lipoproteins; risk factors.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adult
  • Aged
  • Atherosclerosis / blood*
  • Atherosclerosis / genetics*
  • Biomarkers / blood
  • Cell Line, Tumor
  • Cholesterol, HDL / blood*
  • DNA Methylation*
  • Epigenesis, Genetic*
  • Epigenomics / methods
  • Female
  • Genetic Loci*
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Homeodomain Proteins / genetics
  • Humans
  • Macrophages / metabolism*
  • Male
  • Middle Aged
  • Period Circadian Proteins / genetics
  • Peroxisome-Targeting Signal 1 Receptor
  • Phenotype
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Receptors, GABA-A / genetics
  • Spain

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers
  • CMIP protein, human
  • Cholesterol, HDL
  • GABRR1 protein, human
  • HOXA3 protein, human
  • Homeodomain Proteins
  • PER3 protein, human
  • PEX5 protein, human
  • Period Circadian Proteins
  • Peroxisome-Targeting Signal 1 Receptor
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, GABA-A