AccScience Publishing / EJMO / Online First / DOI: 10.36922/EJMO025140077
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ORIGINAL RESEARCH ARTICLE

Causal relationships between mitochondrial DNA copy number and hypertensive disorders in pregnancy: A Mendelian randomization study

Lunzhi Liu1 ,  Ao Wang2 ,  Ke Yi1,2*
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1 Department of Nephrology, Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Diseases / Hubei Provincial Clinical Research Center for Nephrology, Minda Hospital of Hubei Minzu University, Hubei Minzu University, Enshi, Hubei, China
2 Key Laboratory of Obstetrics and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
EJMO, 025140077 https://doi.org/10.36922/EJMO025140077
Received: 31 March 2025 | Revised: 28 April 2025 | Accepted: 15 May 2025 | Published online: 1 July 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Introduction: The association between mitochondrial DNA (mtDNA) copy number and hypertensive disorders in pregnancy has been explored in several observational studies; however, due to methodological limitations and confounding factors, consistent conclusions have not been reached. Objectives: This study aimed to determine whether genetically predicted mtDNA copy number has a causal effect on the risk of hypertensive disorders in pregnancy using Mendelian randomization (MR) analysis. Methods: MR analyses were performed to assess genetic relationships and potential causal associations among four hypertensive pregnancy outcomes: Pre-existing hypertension complicating pregnancy, gestational hypertension, pre-eclampsia or eclampsia (POE), and pre-eclampsia (PE). The mtDNA copy number for each outcome was obtained from genome-wide association study datasets. The primary MR method was inverse variance weighting (IVW), supported by four complementary approaches (MR-Egger, weighted median, simple mode, and weighted mode) to ensure robust inference. Results: IVW analysis revealed a significant inverse correlation between mtDNA copy number and both POE (odds ratio [OR] 95% confidence interval [CI] = 0.738 [0.578 – 0.943]; p=0.015) and PE (OR [95% CI] = 0.735 [0.563 – 0.960]; p=0.024), suggesting a protective effect of higher mtDNA copy number. Conclusion: This MR investigation demonstrates a positive causal relationship between higher mtDNA copy number and reduced risk of PE and related hypertensive disorders in pregnancy.

Keywords
Hypertensive disorders in pregnancy
Mitochondrial DNA copy number
Mendelian randomization
Single nucleotide polymorphism
Instrumental variable
Funding
None.
Conflict of interest
The authors declare there are no competing interests, including potential ones, to disclose in relation to the publication of this paper.
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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