DNA methylation levels are independently associated with prevalence of atherosclerotic cardiovascular disease in multifactorial chylomicronemia syndrome.

BACKGROUND

Multifactorial chylomicronemia syndrome (MCS) is a form of severe hypertriglyceridemia (sHTG) associated with increased risk of acute pancreatitis and atherosclerotic cardiovascular disease (ASCVD). We recently reported suggestive evidence that DNA methylation (DNAm) contribute to the sHTG phenotype in MCS. While few predictors of acute pancreatitis were previously identified in MCS, predictors of ASCVD in MCS remain mostly unknown.

OBJECTIVE

To study the factors associated with previous history of ASCVD in MCS patients.

METHODS

A total of 114 patients with MCS were included in this retrospective study. Prevalence of ASCVD was determined at the baseline visit and defined as any atherosclerotic event: angina, myocardial infarction, coronary angioplasty, coronary bypass surgery, claudication, peripheral angioplasty, peripheral arterial surgery, transient ischemic attack, stroke, carotid endarterectomy, and artery stenosis (>50 %). DNAm level at ABCG1 (cg06500161), CPT1A (cg00574958), and SREBF1 (cg11024682) candidate gene loci was quantified using pyrosequencing of bisulfite-treated DNA.

RESULTS

Univariate analysis showed that age, ABCG1 and SREBF1 DNAm level, and the presence of obesity, hypertension, diabetes, and maximal TG level > 40 mmol/L were associated with previous history of ASCVD. Multivariate analysis showed that age (OR 1.11 [1.04-1.18], p = 0.0006), SREBF1 DNAm levels (OR 1.12 [1.03-1.24], p = 0.01), the presence of a maximal TG level > 40 mmol/L (OR 0.13 [0.02-0.90], p = 0.04), and obesity (OR 3.32 [1.00-11.19, p = 0.05] were independently associated with history of ASCVD and explained 44.8 % of the variability in the prevalence of ASCVD (p < 0.0001).

CONCLUSION

This study shows that SREBF1 DNAm levels are independently associated with prevalence of ASCVD in MCS patients. It suggests that further studies of epivariations may contribute to better understand the clinical heterogeneity seen in MCS patients.