Priyanka Sharma1, Gaurav Garg2, Arun Kumar2, Farhan Mohammad2, Sudha Ramesh Kumar1, Vinay Singh Tanwar2, Satish Sati2, Abhay Sharma2, Ganesan Karthikeyan3, Vani Brahmachari4, Shantanu Sengupta5. 1. CSIR - Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007, India; Dr. B. R. Ambedkar Centre for Biomedical Research, University of Delhi, Delhi 110007, India. 2. CSIR - Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007, India. 3. All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India. 4. Dr. B. R. Ambedkar Centre for Biomedical Research, University of Delhi, Delhi 110007, India. Electronic address: vbrahmachari@acbr.du.ac.in. 5. CSIR - Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007, India. Electronic address: shantanus@igib.res.in.
Abstract
BACKGROUND: The alteration in the epigenome forms an interface between the genotype and the environment. Epigenetic alteration is expected to make a significant contribution to the development of cardiovascular disease where environmental interactions play a key role in disease progression. We had previously shown that global DNA hypermethylation per se is associated with coronary artery disease (CAD) and is further accentuated by high levels of homocysteine, a thiol amino acid which is an independent risk factor for cardiovascular disease and is also a key modulator of macromolecular methylation. RESULTS: We have identified 72 differentially methylated regions (DMRs) that were hypermethylated in CAD patients in the background of varying homocysteine levels. Following deep bisulfite sequencing of a few of the selected DMRs, we found significantly higher methylation in CAD cases. We get six CpG sites in three DMRs that included the intronic region of C1QL4 gene and upstream region of CCDC47 and TGFBR3 genes. CONCLUSION: To the best of our knowledge, this is the first study to identify hypermethylated regions across the genome in patients with coronary artery disease. Further validation in different populations is necessary for this information to be used for disease risk assessment and management.
BACKGROUND: The alteration in the epigenome forms an interface between the genotype and the environment. Epigenetic alteration is expected to make a significant contribution to the development of cardiovascular disease where environmental interactions play a key role in disease progression. We had previously shown that global DNA hypermethylation per se is associated with coronary artery disease (CAD) and is further accentuated by high levels of homocysteine, a thiol amino acid which is an independent risk factor for cardiovascular disease and is also a key modulator of macromolecular methylation. RESULTS: We have identified 72 differentially methylated regions (DMRs) that were hypermethylated in CAD patients in the background of varying homocysteine levels. Following deep bisulfite sequencing of a few of the selected DMRs, we found significantly higher methylation in CAD cases. We get six CpG sites in three DMRs that included the intronic region of C1QL4 gene and upstream region of CCDC47 and TGFBR3 genes. CONCLUSION: To the best of our knowledge, this is the first study to identify hypermethylated regions across the genome in patients with coronary artery disease. Further validation in different populations is necessary for this information to be used for disease risk assessment and management.
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