Genome wide DNA methylation profiling for epigenetic alteration in coronary artery disease patients

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• 作者：Priyanka Sharma^a ; ^b ; Gaurav Garg^a ; Arun Kumar^a ; Farhan Mohammad^a ; Sudha Ramesh Kumar^a ; ^b ; Vinay Singh Tanwar^a ; Satish Sati^a ; Abhay Sharma^a ; Ganesan Karthikeyan^c ; Vani Brahmachari^b ; ^{vbrahmachari@acbr.du.ac.in" class="auth_mail} ; ^{vani.brahmachari@gmail.com" class="auth_mail} ; Shantanu Sengupta^a ; ^{shantanus@igib.res.in" class="auth_mail}
• 关键词：CAD ; coronary artery disease ; DMRs ; differentially methylated regions ; CVD ; cardiovascular disease
• 刊名：Gene
• 出版年：10 May, 2014
• 年：2014
• 卷：541
• 期：1
• 页码：31-40
• 全文大小：775 K

文摘

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.