Integrated analysis of DNA methylation profile of HLA-G gene and imaging in coronary heart disease: Pilot study

PLoS One. 2020 Aug 13;15(8):e0236951. doi: 10.1371/journal.pone.0236951. eCollection 2020.


Aims: Immune endothelial inflammation, underlying coronary heart disease (CHD) related phenotypes, could provide new insight into the pathobiology of the disease. We investigated DNA methylation level of the unique CpG island of HLA-G gene in CHD patients and evaluated the correlation with cardiac computed tomography angiography (CCTA) features.

Methods: Thirty-two patients that underwent CCTA for suspected CHD were enrolled for this study. Obstructive CHD group included fourteen patients, in which there was a stenosis greater than or equal to 50% in one or more of the major coronary arteries detected; whereas subjects with Calcium (Ca) Score = 0, uninjured coronaries and with no obstructive CHD (no critical stenosis, NCS) were considered as control subjects (n = 18). For both groups, DNA methylation profile of the whole 5'UTR-CpG island of HLA-G was measured. The plasma soluble HLA-G (sHLA-G) levels were detected in all subjects by specific ELISA assay. Statistical analysis was performed using R software.

Results: For the first time, our study reported that 1) a significant hypomethylation characterized three specific fragments (B, C and F) of the 5'UTR-CpG island (p = 0.05) of HLA-G gene in CHD patients compared to control group; 2) the hypomethylation level of one specific fragment of 161bp (+616/+777) positively correlated with coronary Ca score, a relevant parameter of CCTA (p<0.05) between two groups evaluated and was predictive for disease severity.

Conclusions: Reduced levels of circulating HLA-G molecules could derive from epigenetic marks. Epigenetics phenomena induce hypomethylation of specific regions into 5'UTR-CpG island of HLA-G gene in CHD patients with obstructive non critical stenosis vs coronary stenosis individuals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions
  • Adult
  • Aged
  • Calcium / metabolism
  • Case-Control Studies
  • Computed Tomography Angiography
  • Coronary Disease / diagnostic imaging
  • Coronary Disease / genetics*
  • Coronary Disease / immunology*
  • Coronary Stenosis / diagnostic imaging
  • Coronary Stenosis / genetics
  • Coronary Stenosis / immunology
  • Coronary Vessels / diagnostic imaging
  • Coronary Vessels / immunology
  • Coronary Vessels / metabolism
  • CpG Islands
  • DNA Methylation*
  • Epigenesis, Genetic
  • Female
  • HLA-G Antigens / blood
  • HLA-G Antigens / genetics*
  • Humans
  • Male
  • Middle Aged
  • Pilot Projects
  • Plaque, Atherosclerotic / diagnostic imaging


  • 5' Untranslated Regions
  • HLA-G Antigens
  • Calcium

Grants and funding

This work was supported by PRIN2017F8ZB89 from “Italian Ministry of University and Research (MIUR)” (PI Prof Napoli) and Ricerca Corrente (RC) 2019 from “Italian Ministry of Health” (PI Prof. Napoli).; by grants GR-2016-02364785 from “Italian Ministry of Health” (PI Dr. Grimaldi).