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

Concetta Schiano, Giuditta Benincasa, Teresa Infante, Monica Franzese, Rossana Castaldo, Carmela Fiorito, Gelsomina Mansueto, Vincenzo Grimaldi, Giovanni Della Valle, Gerardo Fatone, Andrea Soricelli, Giovanni Francesco Nicoletti, Antonio Ruocco, Ciro Mauro, Marco Salvatore, Claudio Napoli

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)e0236951
JournalPLoS ONE
Volume15
Issue number8
DOIs
Publication statusPublished - 2020

Keywords

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

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