The role of control region mitochondrial DNA mutations in cardiovascular disease: stroke and myocardial infarction

Umbria, Miriam; Ramos, Ariel Delgado; Aluja, María Pilar; Santos, Cristina

doi:10.1101/382374

Cited by 3 publications

(4 citation statements)

References 45 publications

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“…Therefore a non-coding control region variant, such as m.73A > G, will not directly affect the oxidative phosphorylation system altering energy or ROS production but, by changing a regulatory motif or being adjacent to one, it may impact the replication and transcription of the mitochondrial genome e.g. slightly influencing mtDNA copy number or gene expression (Suissa et al 2009;Lott et al 2013;Umbria et al 2018). This together with other risk factors and m.11778G > A mutation may possibly modulate the LHON phenotype.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial genome variation in male LHON patients with the m.11778G > A mutation

et al. 2020

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Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder with symptoms limited to a single tissue, optic nerve, resulting in vision loss. In the majority of cases it is caused by one of three point mutations in mitochondrial DNA (mtDNA) but their presence is not sufficient for disease development, since ~50% of men and ~10% women who carry them are affected. Thus additional modifying factors must exist. In this study, we use next generation sequencing to investigate the role of whole mtDNA variation in male Polish patients with LHON and m.11778G > A, the most frequent LHON mutation. We present a possible association between mtDNA haplogroup K and variants in its background, a combination of m.3480A > G, m.9055G > A, m.11299 T > C and m.14167C > T, and LHON mutation. These variants may have a negative effect on m.11778G > A increasing its penetrance and the risk of LHON in the Polish population. Surprisingly, we did not observe associations previously reported for m.11778G > A and LHON in European populations, particularly for haplogroup J as a risk factor, implying that mtDNA variation is much more complex. Our results indicate possible contribution of novel combination of mtDNA genetic factors to the LHON phenotype.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial genome variation in male LHON patients with the m.11778G > A mutation

et al. 2020

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“…Indeed, it has been demonstrated that environmental exposures, contributing to the onset of new mutations or oxidative damages or modulating epigenetic features of mtDNA, strongly impact mitochondrial health. In the light of this evidence, mtDNA depletion and malfunction have been implicated in cancer [ 62 , 63 ], metabolic and cardiovascular diseases [ 43 , 64 , 65 , 66 , 67 ], aging [ 68 ], and many human multifactorial disorders, including neurodegeneration [ 69 , 70 ].…”

Section: Mitochondrial Dna: From Genetics To Epigeneticsmentioning

confidence: 99%

Mitochondrial DNA and Neurodegeneration: Any Role for Dietary Antioxidants?

Bordoni

Gabbianelli

2020

Antioxidants

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The maintenance of the mitochondrial function is essential in preventing and counteracting neurodegeneration. In particular, mitochondria of neuronal cells play a pivotal role in sustaining the high energetic metabolism of these cells and are especially prone to oxidative damage. Since overproduction of reactive oxygen species (ROS) is involved in the pathogenesis of neurodegeneration, dietary antioxidants have been suggested to counteract the detrimental effects of ROS and to preserve the mitochondrial function, thus slowing the progression and limiting the extent of neuronal cell loss in neurodegenerative disorders. In addition to their role in the redox-system homeostasis, mitochondria are unique organelles in that they contain their own genome (mtDNA), which acts at the interface between environmental exposures and the molecular triggers of neurodegeneration. Indeed, it has been demonstrated that mtDNA (including both genetics and, from recent evidence, epigenetics) might play relevant roles in modulating the risk for neurodegenerative disorders. This mini-review describes the link between the mitochondrial genome and cellular oxidative status, with a particular focus on neurodegeneration; moreover, it provides an overview on potential beneficial effects of antioxidants in preserving mitochondrial functions through the protection of mtDNA.

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“…The MtDNA control region is important for controlling mtDNA gene expression. Umbria and colleagues studied mutations in the mtDNA control region in 154 stroke cases and 211 myocardial infarction (MI) patients [129] .…”

Section: Mitochondria and Cardiovascular Diseasesmentioning

confidence: 99%

“…They found that the m.16145 G>A and m.16311 T> C variants could be risk factors for stroke (conditional logistic regression, P = 0.038 & P = 0.018, respectively), and that the m.72 T>C and m.73 A>G variants may be protective against MI (conditional logistic regression, P = 0.001 & P = 0.009, respectively) [129] . ROS molecules are very harmful and may damage macromolecules, such as proteins, lipids and DNA [130] .…”

Section: Mitochondria and Cardiovascular Diseasesmentioning

confidence: 99%

Advancement in the diagnosis of mitochondrial diseases

Sulaiman¹,

Rani²,

Radin³

et al. 2020

JTGG

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Mitochondrial diseases are multi-systemic, heterogeneous groups of diseases that are associated with various neuromuscular problems, cardiovascular disorders, metabolic syndrome, cancer, and obesity. Mitochondrial diseases are due to mutations in mitochondrial DNA or nuclear DNA that can affect the assembly of the mitochondrial components and mitochondrial function. Typically, mitochondrial diseases can be inherited through an autosomal dominant, autosomal recessive or X-linked pattern of inheritance. To date, there are more than 100 mitochondrial diseases identified. However, clinical phenotype heterogeneity is a huge problem for the diagnosis of mitochondrial diseases, as patients with the same mutations exhibit different clinical symptoms. Also, the heteroplasmy/homoplasmy conditions complicate the diagnosis process. Here, in this review, we discuss these challenges and problems in mitochondrial disease diagnosis, focusing on the mutational profile of both primary and secondary mitochondrial diseases. We also review the utilization of next-generation technology and multi-omics strategy to improve the diagnosis. The discussion addresses the current evidence of those applications and the challenges that need some improvement for better diagnosis yield.

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The role of control region mitochondrial DNA mutations in cardiovascular disease: stroke and myocardial infarction

Cited by 3 publications

References 45 publications

Mitochondrial genome variation in male LHON patients with the m.11778G > A mutation

Mitochondrial genome variation in male LHON patients with the m.11778G > A mutation

Mitochondrial DNA and Neurodegeneration: Any Role for Dietary Antioxidants?

Advancement in the diagnosis of mitochondrial diseases

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