title: Detection of altered global DNA methylation in coronary artery disease patients.
abstract: Epigenetic modifications, especially alteration in DNA methylation, are increasingly being recognized as a key factor in the pathogenesis of complex disorders, including atherosclerosis. However, there are limited data on the epigenetic changes in the coronary artery disease (CAD) patients. In the present study we evaluated the methylation status of genomic DNA from peripheral lymphocytes in a cohort of 287 individuals: 137 angiographically confirmed CAD patients and 150 controls. The differential susceptibility of genomic DNA to methylation-sensitive restriction enzymes was utilized to assess the methylation status of the genome. We observed that the genomic DNA methylation in CAD patients is significantly higher than in controls (p < 0.05). Since elevated homocysteine levels are known to be an independent risk factor for CAD and a key modulator of macromolecular methylation, we investigated the probable correlation between plasma homocysteine levels and global DNA methylation. We observed a significant positive correlation of global DNA methylation with plasma homocysteine levels in CAD patients (p = 0.001). Further, within a higher range of serum homocysteine levels (>/=12-50 muM), global DNA methylation was significantly higher in CAD patients than in controls. The alteration in genomic DNA methylation associated with cardiovascular disease per se appears to be further accentuated by higher homocysteine levels.
authors.affiliation: Institute of Genomics and Integrative Biology, Delhi, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Sharma
authors.forename: Jitender
authors.initials: J
authors.lastname: Kumar
authors.forename: Gaurav
authors.initials: G
authors.lastname: Garg
authors.forename: Arun
authors.initials: A
authors.lastname: Kumar
authors.forename: Ashok
authors.initials: A
authors.lastname: Patowary
authors.forename: Ganesan
authors.initials: G
authors.lastname: Karthikeyan
authors.forename: Lakshmy
authors.initials: L
authors.lastname: Ramakrishnan
authors.forename: Vani
authors.initials: V
authors.lastname: Brahmachari
authors.forename: Shantanu
authors.initials: S
authors.lastname: Sengupta
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics / Q000502:physiology; D001057:Apolipoproteins E / Q000235:genetics; D016022:Case-Control Studies; D002874:Chromosome Mapping; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics*; D019175:DNA Methylation; D004032:Diet; D015894:Genome, Human; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008875:Middle Aged
chemical_list: D001057:Apolipoproteins E; D006710:Homocysteine