Abstract 13869: The Association Between DYRK4 Hypomethylation in Peripheral Blood and Coronary Heart Disease: A Case-Control Study

Abstract

Backgrounds: Coronary heart disease (CHD) is a leading cause of morbidity and mortality worldwide, with myocardial infarction (MI) representing its most prevalent type. Previous studies have suggested an association between the dual-specificity tyrosine-regulated kinases ( DYRK) gene family and various cardiovascular disease risks. However, the specific role of DYRK4 in CHD, particularly in MI, remains unclear. Objective: We hereby investigated the association between blood-based DYRK4 methylation and CHD, MI and non-MI related CHD. Methods: A total of 88 CHD cases (23 MI and 65 non-MI) were diagnosed by coronary angiography and clinical presentation at Chinese People's Liberation Army General Hospital from 2018 to 2019. 93 persons who participated in the annual health examination were randomly selected as controls. The DYRK4 methylation, which contains three measurable CpG sites, was quantified by mass spectrometry of nucleic acid. Covariates-adjusted odds ratios (ORs) for -10% methylation was calculated by binary logistic regression, and receiver operating characteristic (ROC) curves were generated to evaluate the discriminatory power. Results: Decreased methylation of DYRK4_CpG_2 and DYRK4_CpG_3 in peripheral blood was significantly associated with increased CHD risk (OR: 1.49 and 1.20; p = 0.044 and 0.049). Notably, these two CpG sites were only significant in non-MI related CHD (OR: 1.71 and 1.33; p = 0.015 and 0.009) rather than MI (OR: 1.11 and 0.99; p = 0.759 and 0.968). The combination of DYRK4_CpG_2 and DYRK4_CpG_3 methylation levels could efficiently discriminate CHD, MI and non-MI related CHD patients from controls (area under curve (AUC) = 0.771, 0.795 and 0.784, respectively). Conclusion: Our study suggests that hypomethylation of DYRK4_CpG_2, DYRK4_CpG_3 in blood is associated with CHD, and DYRK4 methylation model may provide a new strategy for detection of CHD, especially non-MI related CHD.