Abstract 20043: MAOA Methylation is Associated with Subclinical Atherosclerosis in a Monozygotic Twin Sample
Background: The etiology of coronary atherosclerosis involves both gene and environment. Epigenetic changes have been suggested as a mechanism mediating the effects of environmental factors on disease. Monoamine oxidase A (MAOA) gene regulates the metabolism of food intake and energy expenditure and has been associated with CVD risk factors. No study has examined the potential impact of MAOA gene methylation level on vulnerability for atherosclerosis.
Methods: We studied 83 monozygotic male twin pairs drawn from the VETR who were born between 1946 and 1956 (mean age 54). Carotid intima-media thickness (IMT), a surrogate marker for atherosclerosis, was measured by ultrasound. The percentages of DNA methylation at seven CpG sites in the MAOA gene promoter region were quantitatively measured by pyrosequencing. Generalized estimating equation models were used to evaluate the potential associations of DNA methylation level at each single CpG site and of the mean methylation level at this locus with carotid IMT, adjusting for known risk factors including age, smoking, BMI, history of diabetes, and history of hypertension.
Results: DNA methylation levels at six out of the seven studied CpG sites showed significant individual association with early atherosclerosis (p <0.03 at two sites, all other sites p<0.003). The mean DNA methylation level at this locus was also significantly associated with early atherosclerosis (p = 0.0027). On average, a 10% increase in the mean MAOA methylation level was associated with a decrease of 0.112 mm (95% CI: 0.075, 0.149) in carotid IMT. All associations persisted after adjustment for multiple coronary risk factors.
Conclusions: DNA methylation level in the promoter region of the MAOA locus was associated with the risk of early atherosclerosis independent of traditional cardiovascular risk factors. Increased DNA methylation level at this locus was associated with decreased carotid IMT.
- © 2010 by American Heart Association, Inc.