Τίτλος:
Epigenetics-by-Sex Interaction for Coronary Artery Disease Risk Conferred by the Cystathionine γ-Lyase Gene Promoter Methylation
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Coronary artery disease (CAD) is a major global health burden whereby gene-by-environment-by-sex interactions play an important role. Coronary artery bypass graft (CABG) surgery involves patients with well-documented and severe CAD. Hence, the study of CAD in a context of the CABG surgery serves as an advantageous model for disease phenotype ascertainment and genetic association studies. We report here new observations from a case-control genetic association study on promoter methylation of the cystathionine γ-lyase (CTH) gene and its association with CAD. To the best of our knowledge, this is the first clinical study to show the DNA methylation status of the CTH promoter in relation to this clinical phenotype. CTH encodes for the hydrogen sulfide generating enzyme named CSE in the endothelium that is mechanistically highly relevant for CAD. In a sample of 334 subjects from Greece (178 cases with CAD and who underwent CABG, and 156 controls), CTH promoter methylation was analyzed using a SYBR Green-based quantitative methylation-specific polymerase chain reaction. We found increased methylation in CTH promoter in cases (19.1%) compared to controls (10.3%) (p = 0.024). Gene-by-sex analysis sustained the significant association in men (p = 0.032) but not in women (p = 0.884). By using multivariate analyses after controlling for potential confounders such as smoking, age, and gender, we found that increased CTH gene promoter methylation was associated with CAD in the total sample (odds ratio [OR] = 2.163, 95% confidence interval [CI] 1.038-4.506, p = 0.039) and in men (OR = 2.418, 95% CI 1.048-5.581, p = 0.039) but not in women (OR = 0.542, 95% CI 0.094-3.140, p = 0.495). These observations collectively warrant further precision medicine and biomarker research to examine the CTH methylation status as a putative epigenetic regulator of CAD risk in larger and independent samples. © Copyright 2017, Mary Ann Liebert, Inc.
Συγγραφείς:
Giannakopoulou, E.
Konstantinou, F.
Ragia, G.
Tavridou, A.
Karaglani, M.
Chatzaki, E.
Papapetropoulos, A.
Mikroulis, D.
Manolopoulos, V.G.
Περιοδικό:
OMICS: A Journal of Integrative Biology
Εκδότης:
MARY ANN LIEBERT INC PUBL
Λέξεις-κλειδιά:
antihypertensive agent; beta adrenergic receptor blocking agent; calcium channel blocking agent; cholesterol; cystathionine gamma lyase; genomic DNA; glucose; high density lipoprotein cholesterol; hydrogen sulfide; low density lipoprotein cholesterol; nitric acid derivative; triacylglycerol; cystathionine gamma lyase, adult; age; aged; Article; case control study; clinical study; comparative study; controlled study; coronary artery bypass graft; coronary artery disease; coronary risk; disease association; DNA methylation; endothelium; epigenetics; female; gene interaction; genetic analysis; genetic association study; genetic risk; Greece; human; major clinical study; male; patient risk; phenotypic variation; polymerase chain reaction; priority journal; promoter region; quantitative analysis; risk assessment; risk factor; sex difference; smoking; coronary artery disease; DNA methylation; genetic epigenesis; genetics; promoter region; single nucleotide polymorphism, Coronary Artery Disease; Cystathionine gamma-Lyase; DNA Methylation; Epigenesis, Genetic; Female; Genetic Association Studies; Humans; Male; Polymorphism, Single Nucleotide; Promoter Regions, Genetic
DOI:
10.1089/omi.2017.0149
