BACKGROUND: Atherosclerosis is a complex process involving both genetic and 
epigenetic factors. The monoamine oxidase A (MAOA) gene regulates the metabolism 
of key neurotransmitters and has been associated with cardiovascular risk 
factors. This study investigates whether MAOA promoter methylation is associated 
with atherosclerosis, and whether this association is confounded by familial 
factors in a monozygotic (MZ) twin sample.
METHODS: We studied 84 monozygotic (MZ) twin pairs drawn from the Vietnam Era 
Twin Registry. Carotid intima-media thickness (IMT) was measured by ultrasound. 
DNA methylation in the MAOA promoter region was quantified by bisulfite 
pyrosequencing using genomic DNA isolated from peripheral blood leukocytes. The 
association between DNA methylation and IMT was first examined by generalized 
estimating equation, followed by matched pair analyses to determine whether the 
association was confounded by familial factors.
RESULTS: When twins were analyzed as individuals, increased methylation level 
was associated with decreased IMT at four of the seven studied CpG sites. 
However, this association substantially reduced in the matched pair analyses. 
Further adjustment for MAOA genotype also considerably attenuated this 
association.
CONCLUSIONS: The association between MAOA promoter methylation and carotid IMT 
is largely explained by familial factors shared by the twins. Because twins 
reared together share early life experience, which may leave a long-lasting 
epigenetic mark, aberrant MAOA methylation may represent an early biomarker for 
unhealthy familial environment. Clarification of familial factors associated 
with DNA methylation and early atherosclerosis will provide important 
information to uncover clinical correlates of disease.