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Genotyping Single Nucleotide Polymorphisms in the Mitochondrial Genome by Pyrosequencing
Published on: February 10, 2023
Mitochondrial DNA variability and Covid-19 in the Slovak population
Gabriela Bľandová1, Nikola Janoštiaková1, Dominik Kodada1
1Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University, Bratislava, Slovakia.
Abstract:
Recent studies have shown that mitochondria are involved in the pathogenesis of Covid-19. Mitochondria play a role in production of reactive oxygen species and induction of an innate immune response, both important during infections. Common variability of mitochondrial DNA (mtDNA) can affect oxidative phosphorylation and the risk or lethality of cardiovascular, neurodegenerative diseases and sepsis. However, it is unclear whether susceptibility of severe Covid-19 might be affected by mtDNA variation. Thus, we have analyzed mtDNA in a sample of 446 Slovak patients hospitalized due to Covid-19 and a control population group consisting of 1874 individuals. MtDNA variants in the HVRI region have been analyzed and classified into haplogroups at various phylogenetic levels. Binary logistic regression was used to assess the risk of Covid-19. Haplogroups T1, H11, K and variants 16256C > T, 16265A > C, 16293A > G, 16311 T > C and 16399A > G were associated with an increased Covid-19 risk. On contrary, Haplogroup J1, haplogroup clusters H + U5b and T2b + U5b, and the mtDNA variant 16189 T > C were associated with decreased risk of Covid-19. Following the application of the Bonferroni correction, statistical significance was observed exclusively for the cluster of haplogroups H + U5b. Unsurprisingly, the most significant factor contributing to the mortality of patients with Covid-19 is the age of patients. Our findings suggest that mtDNA haplogroups can play a role in Covid-19 pathogenesis, thus potentially useful in identifying susceptibility to its severe form. To confirm these associations, further studies taking into account the nuclear genome or other non-biological influences are needed.
Insights
Mitochondrial DNA (mtDNA) variations influence Covid-19 risk. Certain mtDNA haplogroups, like H+U5b, are linked to reduced susceptibility, while others may increase it, suggesting a role in disease pathogenesis.
Area of Science:
- Genetics and Molecular Biology
- Infectious Diseases
- Human Physiology
Background:
- Mitochondria are implicated in Covid-19 pathogenesis, influencing reactive oxygen species production and innate immune responses.
- Mitochondrial DNA (mtDNA) variability affects susceptibility to various diseases, but its role in severe Covid-19 is not well understood.
Purpose of the Study:
- To investigate the association between mitochondrial DNA (mtDNA) variation and susceptibility to severe Covid-19 in a Slovak population.
- To identify specific mtDNA haplogroups and variants linked to increased or decreased risk of Covid-19 hospitalization.
Main Methods:
- Analysis of mtDNA variants in the HVRI region from 446 hospitalized Covid-19 patients and 1874 controls.
- Classification of mtDNA variants into haplogroups at various phylogenetic levels.
- Application of binary logistic regression to assess Covid-19 risk, with Bonferroni correction for significance.
Main Results:
- Several mtDNA haplogroups (T1, H11, K) and specific variants were associated with increased Covid-19 risk.
- Haplogroup J1, clusters H+U5b and T2b+U5b, and variant 16189T>C showed decreased Covid-19 risk.
- The H+U5b haplogroup cluster demonstrated statistically significant protection after Bonferroni correction.
Conclusions:
- Mitochondrial DNA haplogroups may influence susceptibility to severe Covid-19.
- Specific mtDNA haplogroups, particularly H+U5b, could be protective against severe disease.
- Further research incorporating nuclear genome and other factors is needed to confirm these findings.
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