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Asllanaj, E.* ; Zhang, X.* ; Ochoa Rosales, C.* ; Nano, J. ; Bramer, W.M.* ; Portilla-Fernandez, E.* ; Braun, K.V.E.* ; Gonzalez-Jaramillo, V.* ; Ahrens, W.* ; Ikram, A.* ; Ghanbari, M.* ; Voortman, T.* ; Franco, O.H.* ; Muka, T.* ; Glisic, M.*

Sexually dimorphic DNA-methylation in cardiometabolic health: A systematic review.

Maturitas 135, 6-26 (2020)
Postprint DOI
Open Access Green
Sex is a major determinant of cardiometabolic risk. DNA methylation (DNAm), an important epigenetic mechanism that differs between sexes, has been associated with cardiometabolic diseases. Therefore, we aimed to systematically review studies in adults investigating sex-specific associations of DNAm with intermediate cardiometabolic traits and incident cardiovascular disease including stroke, myocardial infarction (MI) and coronary heart disease (CHD). Five bibliographic databases were searched from inception to 15 July 2019. We selected 35 articles (based on 30 unique studies) from 17,023 references identified, with a total of 14,020 participants of European, North American or Asian ancestry. Four studies reported sex differences between global DNAm and blood lipid levels and stroke risk. In 25 studies that took a genome wide or candidate gene approach, DNAm at 31 gene sites was associated with sex differences in cardiometabolic diseases. The identified genes were PLA2G7, BCL11A, KDM6A, LIPC, ABCG1, PLTP, CETP, ADD1, CNN1B, HOOK2, GFBP-7,PTPN1, GCK, PTX3, ABCG1, GALNT2, CDKN2B, APOE, CTH, GNASAS, INS, PON1, TCN2, CBS, AMT, KDMA6A, FTO, MAP3K13, CCDC8, MMP-2 and ER-a. Prioritized pathway connectivity analysis associated these genes with biological pathways such as vitamin B12 metabolism, statin pathway, plasma lipoprotein, plasma lipoprotein assembly, remodeling and clearance and cholesterol metabolism. Our findings suggest that DNAm might be a promising molecular strategy for understanding sex differences in the pathophysiology of cardiometabolic diseases and that future studies should investigate the effects of sex on epigenetic mechanisms in cardiometabolic risk. In addition, we emphasize the gap between the translational potential and the clinical utilization of cardiometabolic epigenetics.
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Publication type Article: Journal article
Document type Review
Keywords Dna Methylation ; Type 2 Diabetes ; Coronary Disease ; Myocardial Infarction ; Stroke; Coronary-heart-disease; Genome-wide Association; Essential-hypertension; Epigenetic Regulation; Apolipoprotein-e; Lipid-levels; Cardiovascular-disease; Metabolic Syndrome; Gene-expression; Risk-factors
Language english
Publication Year 2020
HGF-reported in Year 2020
ISSN (print) / ISBN 0378-5122
e-ISSN 0378-5122
Journal Maturitas : The European Menopause Journal
Quellenangaben Volume: 135, Issue: , Pages: 6-26 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place Elsevier House, Brookvale Plaza, East Park Shannon, Co, Clare, 00000, Ireland
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
POF-Topic(s) 30202 - Environmental Health
90000 - German Center for Diabetes Research
Research field(s) Genetics and Epidemiology
PSP Element(s) G-504000-002
G-504000-010
G-501900-401
DOI 10.1016/j.maturitas.2020.02.005
WOS ID WOS:000528163800002
Scopus ID 85079837784
Erfassungsdatum 2020-03-11
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