(2022) Mitochondrial Mutations in Protein Coding Genes of Respiratory Chain Including Complexes Iv, V, And Mt-Trna Genes Are Associated Risk Factors for Congenital Heart Disease. EXCLI Journal. pp. 1306-1330.
![[img]](http://eprints.ssu.ac.ir/style/images/fileicons/text.png) |
Text
EXCLI-21-1306.pdf Download (2MB) |
Abstract
Most studies aiming at unraveling the molecular events associated with cardiac congenital heart disease (CHD) have focused on the effect of mutations occurring in the nuclear genome. In recent years, a significant role has been attributed to mitochondria for correct heart development and maturation of cardiomyocytes. Moreover, numerous heart defects have been associated with nucleotide variations occurring in the mitochondrial genome, affecting mitochondrial functions and cardiac energy metabolism, including genes encoding for subunits of respiratory chain complexes. Therefore, mutations in the mitochondrial genome may be a major cause of heart disease, including CHD, and their identification and characterization can shed light on pathological mechanisms occurring during heart development. Here, we have analyzed mitochondrial genetic variants in previously reported mutational genome hotspots and the flanking regions of mt-ND1, mt-ND2, mt-COXI, mt-COXII, mtATPase8, mt-ATPase6, mt-COXIII, and mt-tRNAs (Ile, Gln, Met, Trp, Ala, Asn, Cys, Tyr, Ser, Asp, and Lys) encoding genes by polymerase chain reaction-single stranded conformation polymorphism (PCR-SSCP) in 200 patients with CHD, undergoing cardiac surgery. A total of 23 mitochondrial variations (5 missense mutations, 8 synonymous variations, and 10 nucleotide changes in tRNA encoding genes) were identified and included 16 novel variants. Additionally, we showed that intracellular ATP was significantly reduced (P=0.002) in CHD patients compared with healthy controls, suggesting that the mutations have an impact on mitochondrial energy production. Functional and structural alterations caused by the mitochondrial nucleotide variations in the gene products were studied in-silico and predicted to convey a predisposing risk factor for CHD. Further studies are necessary to better understand the mechanisms by which the alterations identified in the present study contribute to the development of CHD in patients. © 2022, Leibniz Research Centre for Working Environment and Human Factors. All rights reserved.
| Item Type: | Article |
|---|---|
| Keywords: | adenosine triphosphate; alanine transfer RNA; asparagine transfer RNA; aspartic acid transfer RNA; cyclooxygenase 1; cyclooxygenase 2; cyclooxygenase 3; cysteine transfer RNA; cytochrome c oxidase; glutamine transfer RNA; isoleucine transfer RNA; lysine transfer RNA; methionine transfer RNA; mitochondrial DNA; proton transporting adenosine triphosphate synthase; reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone); serine transfer RNA; succinate dehydrogenase (ubiquinone); transfer RNA; tryptophan transfer RNA; tyrosine transfer RNA, Article; ATPase6 gene; ATPase8 gene; case control study; child; cohort analysis; computer analysis; congenital heart disease; controlled study; COXI gene; COXII gene; COXIII gene; DNA flanking region; female; gene mutation; genetic predisposition; genetic variability; heart development; heart disease risk factor; heart surgery; human; human cell; infant; Iranian people; major clinical study; male; missense mutation; mitochondrial dynamics; mitochondrial energy transfer; mitochondrial gene; mitochondrial genetics; molecular pathology; mutational analysis; ND1 gene; ND2 gene; newborn; nucleic acid base substitution; polymerase chain reaction; respiratory chain; sequence alignment; single strand conformation polymorphism; synonymous substitution |
| Page Range: | pp. 1306-1330 |
| Journal or Publication Title: | EXCLI Journal |
| Volume: | 21 |
| Publisher: | Leibniz Research Centre for Working Environment and Human Factors |
| Depositing User: | ms soheila Bazm |
| URI: | http://eprints.ssu.ac.ir/id/eprint/12612 |
Actions (login required)
 |
View Item |