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

Kavitha Matam, Noor Ahmad Shaik, Sunil Aggarwal, Sameer Diwale, Babajan Banaganapalli, Jumana Yousuf Al-Aama, Ramu Elango, Pragna Rao, Qurratulain Hasan

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)533-540
Number of pages8
JournalMolecular Genetics and Genomics
Volume289
Issue number4
DOIs
Publication statusPublished - 2014

Fingerprint

Atrial Appendage
Mitochondrial DNA
Coronary Artery Disease
Cytochromes b
Mutation
Genes
Transfer RNA
Intergenic DNA
Mitochondrial Genome
Electron Transport Complex III
Mitochondrial Proteins
Missense Mutation
Electron Transport
Cardiac Myocytes
Germ Cells
Computer Simulation
Energy Metabolism
Lysine
Life Style
Nucleotides

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics

Cite this

Matam, Kavitha ; Shaik, Noor Ahmad ; Aggarwal, Sunil ; Diwale, Sameer ; Banaganapalli, Babajan ; Al-Aama, Jumana Yousuf ; Elango, Ramu ; Rao, Pragna ; Hasan, Qurratulain. / Evidence for the presence of somatic mitochondrial DNA mutations in right atrial appendage tissues of coronary artery disease patients. In: Molecular Genetics and Genomics. 2014 ; Vol. 289, No. 4. pp. 533-540.
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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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Evidence for the presence of somatic mitochondrial DNA mutations in right atrial appendage tissues of coronary artery disease patients. / Matam, Kavitha; Shaik, Noor Ahmad; Aggarwal, Sunil; Diwale, Sameer; Banaganapalli, Babajan; Al-Aama, Jumana Yousuf; Elango, Ramu; Rao, Pragna; Hasan, Qurratulain.

In: Molecular Genetics and Genomics, Vol. 289, No. 4, 2014, p. 533-540.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Evidence for the presence of somatic mitochondrial DNA mutations in right atrial appendage tissues of coronary artery disease patients

AU - Matam, Kavitha

AU - Shaik, Noor Ahmad

AU - Aggarwal, Sunil

AU - Diwale, Sameer

AU - Banaganapalli, Babajan

AU - Al-Aama, Jumana Yousuf

AU - Elango, Ramu

AU - Rao, Pragna

AU - Hasan, Qurratulain

PY - 2014

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N2 - 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.

AB - 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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