TY - JOUR
T1 - DNA methylation profiling of CD04+/CD08+ T cells reveals pathogenic mechanisms in increasing hyperglycemia
T2 - PIRAMIDE pilot study
AU - Benincasa, Giuditta
AU - Franzese, Monica
AU - Schiano, Concetta
AU - Marfella, Raffaele
AU - Miceli, Marco
AU - Infante, Teresa
AU - Sardu, Celestino
AU - Zanfardino, Mario
AU - Affinito, Ornella
AU - Mansueto, Gelsomina
AU - Sommese, Linda
AU - Nicoletti, Giovanni Francesco
AU - Salvatore, Marco
AU - Paolisso, Giuseppe
AU - Napoli, Claudio
N1 - Funding Information:
This work was supported by PRIN2017F8ZB89 from “Italian Ministry of University and Research” (MIUR) (PI Prof Napoli); by PRIN2017FM74HK_002 from “Italian Ministry of University and Research” (PI Prof Marfella); by grants GR-2016-02364785 and Ricerca Corrente (RC) 2019 from “Italian Ministry of Health ” (PI Prof. Napoli).
Funding Information:
This work was supported by PRIN2017F8ZB89 from “Italian Ministry of University and Research” ( MIUR ) (PI Prof Napoli); by PRIN2017FM74HK_002 from “Italian Ministry of University and Research” (PI Prof Marfella); by grants GR-2016-02364785 and Ricerca Corrente (RC) 2019 from “Italian Ministry of Health ” (PI Prof. Napoli).
Publisher Copyright:
© The Authors
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12
Y1 - 2020/12
N2 - Background: DNA methylation can play a pathogenic role in the early stages of hyperglycemia linking homeostasis imbalance and vascular damage. Material and methods: We investigated DNA methylome by RRBS in CD04+ and CD08+ 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). Results: Globally, differentially methylated regions (DMRs) were mostly annotated to promoter regions. Hypermethylated DMRs were greater than hypomethylated in CD04+ T cells whereas CD08+ 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. Conclusion: SPARC hypomethylation in CD08+ 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.
AB - Background: DNA methylation can play a pathogenic role in the early stages of hyperglycemia linking homeostasis imbalance and vascular damage. Material and methods: We investigated DNA methylome by RRBS in CD04+ and CD08+ 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). Results: Globally, differentially methylated regions (DMRs) were mostly annotated to promoter regions. Hypermethylated DMRs were greater than hypomethylated in CD04+ T cells whereas CD08+ 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. Conclusion: SPARC hypomethylation in CD08+ 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.
KW - Cardiovascular complications
KW - DNA methylation
KW - Prediabetes
KW - T cells
KW - Type 2 diabetes
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U2 - 10.1016/j.amsu.2020.10.016
DO - 10.1016/j.amsu.2020.10.016
M3 - Article
AN - SCOPUS:85094977707
SN - 2049-0801
VL - 60
SP - 218
EP - 226
JO - Annals of Medicine and Surgery
JF - Annals of Medicine and Surgery
ER -