Abstract 11120: Promoter Methylation of BDNF Gene is Associated with Subclinical Atherosclerosis in a Monozygotic Twin Sample
Background: Epigenetic mechanisms, especially DNA methylation, play an important role in complex human diseases including atherosclerosis. Brain-derived neurotrophic factor (BDNF) gene regulates multiple metabolic processes and is implicated in the pathogenesis of a wide range of cardiometabolic phenotypes. No study has examined the potential impact of methylation variation in the promoter region of BDNF on the susceptibility to subclinical atherosclerosis.
Methods: In a sample of 84 middle-aged, monozygotic male twin pairs, we quantified the percentages of DNA methylation variation at ten CpG sites in the promoter region of BDNF gene by bisulfite pyrosequencing. Flow-mediated dilation (FMD) that estimates endothelial function was measured by brachial ultrasound. FMD has been used as a biomarker for subclinical atherosclerosis. Matched pair analysis was used to evaluate the association between DNA methylation variation at each CpG site and FMD. We adjusted for known cardiovascular risk factors, including smoking, body mass index (BMI), high-density lipoprotein (HDL), low-density lipoprotein (LDL), systolic blood pressure and depressive symptoms.
Results: DNA methylation levels at three adjacent CpG sites showed significant association with FMD (all p ≤0.003). On average, a 1% increase in the within-pair difference in DNA methylation level was associated with 2.9% (95% CI: 0.4, 5.3) decrease in the within-pair difference in FMD. All associations persisted after adjustments for cardiovascular risk factors and multiple testing.
Conclusions: DNA methylation variation in the promoter region of the BDNF locus was associated with subclinical atherosclerosis independent of established cardiovascular risk factors. Increased DNA methylation at this locus was associated with decreased FMD. Given that a higher methylation level may result in lower BDNF expression, our finding supports the cardioprotective effect of this gene reported in previous studies.
- © 2012 by American Heart Association, Inc.