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DNA methylation profiling of CD04 + /CD08 + T cells reveals pathogenic mechanisms in increasing hyperglycemia: PIRAMIDE pilot study.

Authors :
Benincasa G
Franzese M
Schiano C
Marfella R
Miceli M
Infante T
Sardu C
Zanfardino M
Affinito O
Mansueto G
Sommese L
Nicoletti GF
Salvatore M
Paolisso G
Napoli C
Source :
Annals of medicine and surgery (2012) [Ann Med Surg (Lond)] 2020 Oct 20; Vol. 60, pp. 218-226. Date of Electronic Publication: 2020 Oct 20 (Print Publication: 2020).
Publication Year :
2020

Abstract

Background: DNA methylation can play a pathogenic role in the early stages of hyperglycemia linking homeostasis imbalance and vascular damage.<br />Material and Methods: We investigated DNA methylome by RRBS in CD04 <superscript>+</superscript> and CD08 <superscript>+</superscript> T cells from healthy subjects (HS) to pre-diabetics (Pre-Diab) and type 2 diabetic (T2D) patients to identify early biomarkers of glucose impairment and vascular damage. Our cross-sectional study enrolled 14 individuals from HS state to increasing hyperglycemia (pilot study, PIRAMIDE trial, NCT03792607).<br />Results: Globally, differentially methylated regions (DMRs) were mostly annotated to promoter regions. Hypermethylated DMRs were greater than hypomethylated in CD04 <superscript>+</superscript> T cells whereas CD08 <superscript>+</superscript> T showed an opposite trend. Moreover, DMRs overlapping between Pre-Diab and T2D patients were mostly hypermethylated in both T cells. Interestingly, SPARC was the most hypomethylated gene in Pre-Diab and its methylation level gradually decreased in T2D patients. Besides, SPARC showed a significant positive correlation with DBP (+0.76), HDL (+0.54), Creatinine (+0.83), LVDd (+0.98), LVSD (+0.98), LAD (+0.98), LVPWd (+0.84), AODd (+0.81), HR (+0.72), Triglycerides (+0.83), LAD (+0.69) and AODd (+0.52) whereas a negative correlation with Cholesterol (-0.52) and LDL (-0.71) in T2D.<br />Conclusion: SPARC hypomethylation in CD08 <superscript>+</superscript> T cells may be a useful biomarker of vascular complications in Pre-Diab with a possible role for primary prevention warranting further multicenter clinical trials to validate our findings.<br />Competing Interests: The authors declare no conflict of interest.<br /> (© 2020 The Authors.)

Details

Language :
English
ISSN :
2049-0801
Volume :
60
Database :
MEDLINE
Journal :
Annals of medicine and surgery (2012)
Publication Type :
Academic Journal
Accession number :
33194177
Full Text :
https://doi.org/10.1016/j.amsu.2020.10.016