Common mtDNA variations at C5178a and A249d/T6392C/G10310A decrease the risk of severe COVID-19 in a Han Chinese population from Central China

Abstract Background Mitochondria have been shown to play vital roles during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) development. Currently, it is unclear whether mitochondrial DNA (mtDNA) variants, which define mtDNA haplogroups...

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Main Authors: Yi Wu, Xian-Hui Wang, Xi-Hua Li, Li-Yuan Song, Shi-Long Yu, Zhi-Cheng Fang, Yu-Quan Liu, Le-Yong Yuan, Chun-Yan Peng, Shen-Yi Zhang, Wang Cheng, Hong-Chao Ma, Li-Feng Wang, Jun-Ming Tang, Yun-Fu Wang, Fu-Yun Ji
Format: Article
Language:English
Published: BMC 2021-11-01
Series:Military Medical Research
Subjects:
Online Access:https://doi.org/10.1186/s40779-021-00351-2
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author Yi Wu
Xian-Hui Wang
Xi-Hua Li
Li-Yuan Song
Shi-Long Yu
Zhi-Cheng Fang
Yu-Quan Liu
Le-Yong Yuan
Chun-Yan Peng
Shen-Yi Zhang
Wang Cheng
Hong-Chao Ma
Li-Feng Wang
Jun-Ming Tang
Yun-Fu Wang
Fu-Yun Ji
author_facet Yi Wu
Xian-Hui Wang
Xi-Hua Li
Li-Yuan Song
Shi-Long Yu
Zhi-Cheng Fang
Yu-Quan Liu
Le-Yong Yuan
Chun-Yan Peng
Shen-Yi Zhang
Wang Cheng
Hong-Chao Ma
Li-Feng Wang
Jun-Ming Tang
Yun-Fu Wang
Fu-Yun Ji
author_sort Yi Wu
collection DOAJ
description Abstract Background Mitochondria have been shown to play vital roles during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) development. Currently, it is unclear whether mitochondrial DNA (mtDNA) variants, which define mtDNA haplogroups and determine oxidative phosphorylation performance and reactive oxygen species production, are associated with COVID-19 risk. Methods A population-based case–control study was conducted to compare the distribution of mtDNA variations defining mtDNA haplogroups between healthy controls (n = 615) and COVID-19 patients (n = 536). COVID-19 patients were diagnosed based on molecular diagnostics of the viral genome by qPCR and chest X-ray or computed tomography scanning. The exclusion criteria for the healthy controls were any history of disease in the month preceding the study assessment. MtDNA variants defining mtDNA haplogroups were identified by PCR-RFLPs and HVS-I sequencing and determined based on mtDNA phylogenetic analysis using Mitomap Phylogeny. Student’s t-test was used for continuous variables, and Pearson’s chi-squared test or Fisher’s exact test was used for categorical variables. To assess the independent effect of each mtDNA variant defining mtDNA haplogroups, multivariate logistic regression analyses were performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) with adjustments for possible confounding factors of age, sex, smoking and diseases (including cardiopulmonary diseases, diabetes, obesity and hypertension) as determined through clinical and radiographic examinations. Results Multivariate logistic regression analyses revealed that the most common investigated mtDNA variations (> 10% in the control population) at C5178a (in NADH dehydrogenase subunit 2 gene, ND2) and A249d (in the displacement loop region, D-loop)/T6392C (in cytochrome c oxidase I gene, CO1)/G10310A (in ND3) were associated with a reduced risk of severe COVID-19 (OR = 0.590, 95% CI 0.428–0.814, P = 0.001; and OR = 0.654, 95% CI 0.457–0.936, P = 0.020, respectively), while A4833G (ND2), A4715G (ND2), T3394C (ND1) and G5417A (ND2)/C16257a (D-loop)/C16261T (D-loop) were related to an increased risk of severe COVID-19 (OR = 2.336, 95% CI 1.179–4.608, P = 0.015; OR = 2.033, 95% CI 1.242–3.322, P = 0.005; OR = 3.040, 95% CI 1.522–6.061, P = 0.002; and OR = 2.890, 95% CI 1.199–6.993, P = 0.018, respectively). Conclusions This is the first study to explore the association of mtDNA variants with individual’s risk of developing severe COVID-19. Based on the case–control study, we concluded that the common mtDNA variants at C5178a and A249d/T6392C/G10310A might contribute to an individual’s resistance to developing severe COVID-19, whereas A4833G, A4715G, T3394C and G5417A/C16257a/C16261T might increase an individual’s risk of developing severe COVID-19.
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spelling doaj.art-33d8fccb16bf4eedaff444b853677db12022-12-21T20:29:13ZengBMCMilitary Medical Research2054-93692021-11-018111010.1186/s40779-021-00351-2Common mtDNA variations at C5178a and A249d/T6392C/G10310A decrease the risk of severe COVID-19 in a Han Chinese population from Central ChinaYi Wu0Xian-Hui Wang1Xi-Hua Li2Li-Yuan Song3Shi-Long Yu4Zhi-Cheng Fang5Yu-Quan Liu6Le-Yong Yuan7Chun-Yan Peng8Shen-Yi Zhang9Wang Cheng10Hong-Chao Ma11Li-Feng Wang12Jun-Ming Tang13Yun-Fu Wang14Fu-Yun Ji15Department of Medical Biology, School of Basic Medical Science, Hubei University of MedicineInstitute of Biomedical Research, Hubei University of MedicineDepartment of Medical Biology, School of Basic Medical Science, Hubei University of MedicineDepartment of Medical Biology, School of Basic Medical Science, Hubei University of MedicineInstitute of Human Respiratory Disease, Xinqiao Hospital, The Army Medical University (Third Military Medical University)Department of Emergency Medicine, Taihe Hospital, Hubei University of MedicineDepartment of Geriatric Medicine, Taihe Hospital, Hubei University of MedicineDepartment of Immunology, School of Basic Medical Sciences, Hubei University of MedicineDepartment of Laboratory Medicine, Taihe Hospital, Hubei University of MedicineDepartment of Medical Biology, School of Basic Medical Science, Hubei University of MedicineDepartment of Medical Biology, School of Basic Medical Science, Hubei University of MedicineDepartment of Medical Biology, School of Basic Medical Science, Hubei University of MedicineDepartment of Medical Biology, School of Basic Medical Science, Hubei University of MedicineHubei Key Laboratory of Embryonic Stem Cell Research, School of Basic Medical Science, Hubei University of MedicineDepartment of Neurology, Taihe Hospital, Hubei University of MedicineDepartment of Medical Biology, School of Basic Medical Science, Hubei University of MedicineAbstract Background Mitochondria have been shown to play vital roles during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) development. Currently, it is unclear whether mitochondrial DNA (mtDNA) variants, which define mtDNA haplogroups and determine oxidative phosphorylation performance and reactive oxygen species production, are associated with COVID-19 risk. Methods A population-based case–control study was conducted to compare the distribution of mtDNA variations defining mtDNA haplogroups between healthy controls (n = 615) and COVID-19 patients (n = 536). COVID-19 patients were diagnosed based on molecular diagnostics of the viral genome by qPCR and chest X-ray or computed tomography scanning. The exclusion criteria for the healthy controls were any history of disease in the month preceding the study assessment. MtDNA variants defining mtDNA haplogroups were identified by PCR-RFLPs and HVS-I sequencing and determined based on mtDNA phylogenetic analysis using Mitomap Phylogeny. Student’s t-test was used for continuous variables, and Pearson’s chi-squared test or Fisher’s exact test was used for categorical variables. To assess the independent effect of each mtDNA variant defining mtDNA haplogroups, multivariate logistic regression analyses were performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) with adjustments for possible confounding factors of age, sex, smoking and diseases (including cardiopulmonary diseases, diabetes, obesity and hypertension) as determined through clinical and radiographic examinations. Results Multivariate logistic regression analyses revealed that the most common investigated mtDNA variations (> 10% in the control population) at C5178a (in NADH dehydrogenase subunit 2 gene, ND2) and A249d (in the displacement loop region, D-loop)/T6392C (in cytochrome c oxidase I gene, CO1)/G10310A (in ND3) were associated with a reduced risk of severe COVID-19 (OR = 0.590, 95% CI 0.428–0.814, P = 0.001; and OR = 0.654, 95% CI 0.457–0.936, P = 0.020, respectively), while A4833G (ND2), A4715G (ND2), T3394C (ND1) and G5417A (ND2)/C16257a (D-loop)/C16261T (D-loop) were related to an increased risk of severe COVID-19 (OR = 2.336, 95% CI 1.179–4.608, P = 0.015; OR = 2.033, 95% CI 1.242–3.322, P = 0.005; OR = 3.040, 95% CI 1.522–6.061, P = 0.002; and OR = 2.890, 95% CI 1.199–6.993, P = 0.018, respectively). Conclusions This is the first study to explore the association of mtDNA variants with individual’s risk of developing severe COVID-19. Based on the case–control study, we concluded that the common mtDNA variants at C5178a and A249d/T6392C/G10310A might contribute to an individual’s resistance to developing severe COVID-19, whereas A4833G, A4715G, T3394C and G5417A/C16257a/C16261T might increase an individual’s risk of developing severe COVID-19.https://doi.org/10.1186/s40779-021-00351-2MtDNA variationsSARS-CoV-2COVID-19RiskHan Chinese
spellingShingle Yi Wu
Xian-Hui Wang
Xi-Hua Li
Li-Yuan Song
Shi-Long Yu
Zhi-Cheng Fang
Yu-Quan Liu
Le-Yong Yuan
Chun-Yan Peng
Shen-Yi Zhang
Wang Cheng
Hong-Chao Ma
Li-Feng Wang
Jun-Ming Tang
Yun-Fu Wang
Fu-Yun Ji
Common mtDNA variations at C5178a and A249d/T6392C/G10310A decrease the risk of severe COVID-19 in a Han Chinese population from Central China
Military Medical Research
MtDNA variations
SARS-CoV-2
COVID-19
Risk
Han Chinese
title Common mtDNA variations at C5178a and A249d/T6392C/G10310A decrease the risk of severe COVID-19 in a Han Chinese population from Central China
title_full Common mtDNA variations at C5178a and A249d/T6392C/G10310A decrease the risk of severe COVID-19 in a Han Chinese population from Central China
title_fullStr Common mtDNA variations at C5178a and A249d/T6392C/G10310A decrease the risk of severe COVID-19 in a Han Chinese population from Central China
title_full_unstemmed Common mtDNA variations at C5178a and A249d/T6392C/G10310A decrease the risk of severe COVID-19 in a Han Chinese population from Central China
title_short Common mtDNA variations at C5178a and A249d/T6392C/G10310A decrease the risk of severe COVID-19 in a Han Chinese population from Central China
title_sort common mtdna variations at c5178a and a249d t6392c g10310a decrease the risk of severe covid 19 in a han chinese population from central china
topic MtDNA variations
SARS-CoV-2
COVID-19
Risk
Han Chinese
url https://doi.org/10.1186/s40779-021-00351-2
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