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Differential methylation pattern in patients with coronary artery disease: pilot study

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Abstract

Epidemiological studies have revealed that coronary artery disease (CAD) is highly heritable. However, genetic studies have not been able to fully elucidate its etiology. Accumulating evidences suggest that epigenetic alterations like DNA methylation may provide an alternative and additional explanation of its pathophysiology. DNA methylation regulates hypomethylation and hypermethylation of various genes which are involved in the development of CAD. Our aim was to identify differentially methylated regions (DMRs) in genome of CAD patients by using the microarray chip having a coverage of > 4,50,000 CpG sites (Illumina’s Infinium HumanMethylation450 BeadChip). In this pilot study, an epigenome-wide analysis of DNA methylation from whole blood was performed in six angiographically positive male cases, who were age and gender matched with six angiographically negative controls. All subjects were non-smokers, non-diabetic, non-alcoholic, with no previous history of cardiac ailment. Illumina’s GenomeStudio (v 2011.1) software was used to identify DMRs and pathway analysis, gene ontology was carried out using DAVID (Database for Annotation, Visualisation and Integrated Discovery). 429 DMRs were found to be significant of which 222 were hypomethylated and 207 were hypermethylated. Antigen processing and presentation was identified to be the most significant biological function with a statistical significance of p = 4.35 × 10− 5. HLA-DRB1, HLA-DQA1, HLA-DQB1 along with non-classical HLA molecules HLA-G, HLA-C are responsible for triggering the inflammatory pathway which have been identified in our study. To the best of our knowledge, this is the first study to identify a panel of DMRs using a high coverage microarray chip in India.

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Acknowledgements

We are grateful to National Health and Education Society (NHES) for funding the study.

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Authors and Affiliations

  1. Research Laboratories, P. D. Hinduja Hospital & Medical Research Centre, Mumbai, India

    Shyamashree Banerjee & Tester F. Ashavaid

  2. Department of Cardiology, P. D. Hinduja Hospital & Medical Research Centre, Mumbai, India

    Chandrashekhar K. Ponde & Rajesh M. Rajani

  3. Department of Biochemistry, P. D. Hinduja Hospital & Medical Research Centre, Mumbai, India

    Tester F. Ashavaid

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  1. Shyamashree Banerjee
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Correspondence to Tester F. Ashavaid.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Banerjee, S., Ponde, C.K., Rajani, R.M. et al. Differential methylation pattern in patients with coronary artery disease: pilot study. Mol Biol Rep 46, 541–550 (2019). https://doi.org/10.1007/s11033-018-4507-y

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