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Evidence for the presence of somatic mitochondrial DNA mutations in right atrial appendage tissues of coronary artery disease patients

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Abstract

Coronary artery disease (CAD) is a multifactorial disease with the underlying involvement of environment, life style and nuclear genetics. However, the role of extranuclear genetic material in terms of somatically acquired mutations in mitochondrial tRNA and protein coding genes in the initiation or progression of CAD is not well defined. Hence, in the present study, right atrial appendage tissues and matched blood samples of 150 CAD patients were screened for mutations in nucleotide regions encompassing the Cytochrome c oxidase subunit II (MT-CO2), tRNA lysine (MT-TK), ATP synthase F0 subunit 8 (MT-ATP8) and Cytochrome b (MT-CYB) genes of mitochondrial DNA. We have found 9 different somatic mutations in 6 % of the CAD patients. Out of these mutations, 4 each were localized in MT-TK gene (T8324A, A8326G, A8331G and A8344G) and MT-CYB genes (T15062C, C15238A, T15378G and C15491G) in addition to one mutation in non-coding region 7 (A8270T) of mitochondrial genome. In addition, we noticed that majority (85.3 %) of CAD patients showed double repeats of germ-line “CCCCCTCTA” intergenic sequence between MT-CO2 and MT-TK genes. Our in-silico investigations of missense mutations revealed that they may alter the free energy and stability of polypeptide chains of MT-CYB protein of complex III of mitochondrial respiratory chain. Based on our study findings, we hypothesize that the somatically acquired variations in MT-TK and MT-CYB genes may negatively impact the energy metabolism of cardiomyocytes in right atrial appendage tissues and contribute in the cardiac dysfunction among CAD patients. In conclusion, our findings may be likely to have potential implications in understanding the disease pathophysiology, diagnosis as well as for the better therapeutic management of CAD patients.

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Acknowledgments

We would like to thank the patients and their physicians for collaboration with the study. We are grateful to our colleagues in Kamineni Hospitals, Hyderabad for their assistance. Authors also acknowledge Mohammed Kaleemuddin, Researcher at Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders for contributing his part in bioinformatics analysis of the present work. The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Princess Al-Jawhara Albrahim Center of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia

    Noor Ahmad Shaik, Babajan Banaganapalli, Jumana Yousuf Al-Aama & Ramu Elango

  2. Department of Genetics & Molecular Medicine, Kamineni Hospitals, L B Nagar, Hyderabad, India

    Kavitha Matam, Sunil Aggarwal, Sameer Diwale & Qurratulain Hasan

  3. Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia

    Noor Ahmad Shaik & Jumana Yousuf Al-Aama

  4. Department of Genetics, Osmania University, Hyderabad, India

    Kavitha Matam

  5. Department of Biochemistry, Kamineni Institute of Medical Sciences, Narketpally, Nalgonda, Hyderabad, India

    Pragna Rao

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  1. Kavitha Matam
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  2. Noor Ahmad Shaik
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  9. Qurratulain Hasan
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Correspondence to Kavitha Matam.

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Communicated by S. Hohmann.

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Matam, K., Shaik, N.A., Aggarwal, S. et al. Evidence for the presence of somatic mitochondrial DNA mutations in right atrial appendage tissues of coronary artery disease patients. Mol Genet Genomics 289, 533–540 (2014). https://doi.org/10.1007/s00438-014-0828-2

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  • DOI: https://doi.org/10.1007/s00438-014-0828-2

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