Abstract
Recently, a significant epigenetic component in the pathogenesis of Coronary Artery Disease (CAD) has been realized. Here, we evaluated the possible association of candidate Single Nucleotide Polymorphisms (SNPs) in the epigenetic-regulatory gene, DNA methyltransferase 1 (DNMT1), with CAD in Chinese Han population. Five tag SNPs (rs16999593, rs2336691, rs2228611, rs4804494, rs7253062) were analyzed by High Resolution Melt (HRM) method in 476 CAD patients and 478 controls. Overall, there were significant differences in the genotype and allele distributions of rs2228611 and rs2336691, between patients and controls. The minor A allele of rs2228611 was associated with a lower risk of CAD (p = 0.034); modest effect in the additive analysis but also marginal significance was found in the recessive model [ORadditive = 0.404 (0.184, 0.884), p = 0.023 and ORrecessive = 0.452 (0.213, 0.963), p = 0.040] after adjusting for confounders. While the rs2336691 A allele were associated with a higher risk of developing CAD (p = 0.037); borderline significant association in both additive and dominant models [ORadditive = 1.632 (1.030, 2.583), p = 0.037 and ORdominant = 1.599 (1.020, 2.507), p = 0.040]. In conclusion, these data provide the first evidence that occurrence of CAD may be moderated by genetic variation in the gene involved in the epigenetic machinery.
Highlights
DNA methylation is an important cellular mechanism that modulates gene expression associated with aging, inflammation and atherosclerotic processes
Our research provided preliminary evidence that Single Nucleotide Polymorphisms (SNPs) on DNA methyltransferase 1 (DNMT1) were associated with Coronary Artery Disease (CAD)
Expression was associated with increased cellular proliferation in atherosclerosis [5], we speculate that the DNMT1 expression levels might be altered under different genotypes which contributes to the pathological process of CAD
Summary
DNA methylation is an important cellular mechanism that modulates gene expression associated with aging, inflammation and atherosclerotic processes. Artery Disease (CAD) [1,2]. Significant genomic hypomethylation was found both in vivo and in vitro, including aging smooth muscle cells, aortas of apolipoprotein E-knockout (Apo-E-) mice, as well as in advanced human atherosclerotic lesions [3,4,5]. Hypermethylation of certain genes, including estrogen receptor 1 (ER-α), tissue factor pathway inhibitor 2 (TFPI-2), ATP-binding cassette sub-family A member 1 (ABCA1), occurred in vascular tissue or peripheral blood cells in CAD patient [6,7,8]. Promoter hypermethylation of 11 mechanosensitive genes due to disturbed blood flow in carotid artery was identified in mouse [10]. On the basis of these observations, we anticipated that perturbations of DNA methylation contributed to CAD risk variability
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