The landscape of rare mitochondrial DNA variants in sudden cardiac death: A potential role for ATP synthase
Sudden cardiac death (SCD) is a major health concern, which can be the sign of a latent mitochondrial disease. However, mitochondrial DNA (mtDNA) contribution is largely unexplored in SCD at population level. Recently, mtDNA variants have been associated with congenital cardiopathy and higher risk o...
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Elsevier
2025-01-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024176232 |
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| author | Elena Luppi Monica De Luise Carla Bini Guido Pelletti Gaia Tioli Ivana Kurelac Luisa Iommarini Susi Pelotti Giuseppe Gasparre |
| author_facet | Elena Luppi Monica De Luise Carla Bini Guido Pelletti Gaia Tioli Ivana Kurelac Luisa Iommarini Susi Pelotti Giuseppe Gasparre |
| author_sort | Elena Luppi |
| collection | DOAJ |
| description | Sudden cardiac death (SCD) is a major health concern, which can be the sign of a latent mitochondrial disease. However, mitochondrial DNA (mtDNA) contribution is largely unexplored in SCD at population level. Recently, mtDNA variants have been associated with congenital cardiopathy and higher risk of ischemic heart disease, suggesting them as potential risk factors also in SCD. Therefore, we aimed to define the mtDNA mutational landscape in such phenotype, by sequencing the whole blood mtDNA genome in a pilot cohort of 28 unrelated subjects. Coding variants were prioritized according to their population and haplogroup frequency. Out of 28 patients, 36% were diagnosed with coronary artery disease, 39% with structural defects and 25% with unspecified cardiac disease. The overall frequency of macro-haplogroups followed the distribution in the European population. No known or novel mtDNA pathogenic variants were found. Two rRNA and 8 missense variants were rarer than polymorphisms as they had a frequency lower than 1% in population databases. 5/8 missense variants clustered in ATP synthase genes and 4/8 missense variants were previously detected in patients with suspected mitochondriopathy. We concluded that primary mitochondrial disease is not a major cause of SCD, but rare mtDNA variants may occur (35.7% in our cohort vs 0.65% in the population; p < 0.01), potentially modifying the risk. |
| format | Article |
| id | doaj-art-5a63d429b74c4928922823472a98cd97 |
| institution | Kabale University |
| issn | 2405-8440 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj-art-5a63d429b74c4928922823472a98cd972025-01-17T04:51:43ZengElsevierHeliyon2405-84402025-01-01111e41592The landscape of rare mitochondrial DNA variants in sudden cardiac death: A potential role for ATP synthaseElena Luppi0Monica De Luise1Carla Bini2Guido Pelletti3Gaia Tioli4Ivana Kurelac5Luisa Iommarini6Susi Pelotti7Giuseppe Gasparre8Unit of Medical Genetics, Department of Medical and Surgical Sciences, University of Bologna, Bologna, ItalyUnit of Medical Genetics, Department of Medical and Surgical Sciences, University of Bologna, Bologna, ItalyUnit of Legal Medicine, Department of Medical and Surgical Sciences, University of Bologna, Bologna, ItalyUnit of Legal Medicine, Department of Medical and Surgical Sciences, University of Bologna, Bologna, ItalyDepartment of Pharmacy and Biotechnology, University of Bologna, Bologna, ItalyUnit of Medical Genetics, Department of Medical and Surgical Sciences, University of Bologna, Bologna, ItalyDepartment of Pharmacy and Biotechnology, University of Bologna, Bologna, ItalyUnit of Legal Medicine, Department of Medical and Surgical Sciences, University of Bologna, Bologna, ItalyUnit of Medical Genetics, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; Corresponding author. Department of Medical and Surgical Sciences (DIMEC) Medical Genetics Unit, Pad. 11 University of Bologna – Medical School Via Massarenti 9, 40138, Bologna, Italy.Sudden cardiac death (SCD) is a major health concern, which can be the sign of a latent mitochondrial disease. However, mitochondrial DNA (mtDNA) contribution is largely unexplored in SCD at population level. Recently, mtDNA variants have been associated with congenital cardiopathy and higher risk of ischemic heart disease, suggesting them as potential risk factors also in SCD. Therefore, we aimed to define the mtDNA mutational landscape in such phenotype, by sequencing the whole blood mtDNA genome in a pilot cohort of 28 unrelated subjects. Coding variants were prioritized according to their population and haplogroup frequency. Out of 28 patients, 36% were diagnosed with coronary artery disease, 39% with structural defects and 25% with unspecified cardiac disease. The overall frequency of macro-haplogroups followed the distribution in the European population. No known or novel mtDNA pathogenic variants were found. Two rRNA and 8 missense variants were rarer than polymorphisms as they had a frequency lower than 1% in population databases. 5/8 missense variants clustered in ATP synthase genes and 4/8 missense variants were previously detected in patients with suspected mitochondriopathy. We concluded that primary mitochondrial disease is not a major cause of SCD, but rare mtDNA variants may occur (35.7% in our cohort vs 0.65% in the population; p < 0.01), potentially modifying the risk.http://www.sciencedirect.com/science/article/pii/S2405844024176232Sudden cardiac deathMitochondrial genomeM chromosomeMitochondrial haplogroupsSNVsHeart disease |
| spellingShingle | Elena Luppi Monica De Luise Carla Bini Guido Pelletti Gaia Tioli Ivana Kurelac Luisa Iommarini Susi Pelotti Giuseppe Gasparre The landscape of rare mitochondrial DNA variants in sudden cardiac death: A potential role for ATP synthase Heliyon Sudden cardiac death Mitochondrial genome M chromosome Mitochondrial haplogroups SNVs Heart disease |
| title | The landscape of rare mitochondrial DNA variants in sudden cardiac death: A potential role for ATP synthase |
| title_full | The landscape of rare mitochondrial DNA variants in sudden cardiac death: A potential role for ATP synthase |
| title_fullStr | The landscape of rare mitochondrial DNA variants in sudden cardiac death: A potential role for ATP synthase |
| title_full_unstemmed | The landscape of rare mitochondrial DNA variants in sudden cardiac death: A potential role for ATP synthase |
| title_short | The landscape of rare mitochondrial DNA variants in sudden cardiac death: A potential role for ATP synthase |
| title_sort | landscape of rare mitochondrial dna variants in sudden cardiac death a potential role for atp synthase |
| topic | Sudden cardiac death Mitochondrial genome M chromosome Mitochondrial haplogroups SNVs Heart disease |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024176232 |
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