Highlights
- •Epigenetic changes in specific individual genes might be differently associated with cardiometabolic traits in men and women.
- •Robust, replicable results can uncover the molecular biological processes involved in disease onset and progression.
- •More attention to sex in epigenetic studies is needed, which could help our understanding of CVD mechanisms in men and women.
Abstract
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-α. 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.
Keywords
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Article info
Publication history
Published online: February 13, 2020
Accepted:
February 12,
2020
Received in revised form:
February 3,
2020
Received:
December 16,
2019
Identification
Copyright
© 2020 Published by Elsevier B.V.
