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Aims <p>Gestational diabetes mellitus (GDM) is associated with mitochondrial dysfunction. Mitochondrial DNA (mtDNA) plays a critical role in mitochondrial function, affecting cellular oxidative phosphorylation and ATP supply. This study aims to explore the association between mtDNA variations and GDM in Han Chinese women.</p> Methods <p>This nested case-control study was conducted among 701 women who developed GDM and 859 contemporaneous controls based on the Chinese Birth Cohort of Environmental and Genetic Factors between 2018 and 2022. Next-generation sequencing was performed on the samples to detect variations in the whole mitochondrial genome. The sequencing data were analyzed, and the differences in the number of mtDNA variations between the two groups were assessed using a t-test. Haplogroup analysis was conducted through the chi-square test. Logistic regression analysis was performed, adjusting for age, BMI, gravidity, and parity, to identify significantly different mtDNA variations between the two groups.</p> Results <p>Pregnant women with GDM carried fewer mtDNA variants in the D-loop region (11.35 ± 2.77 vs. 11.80 ± 2.86, <i>p</i> = 0.002). Results indicated that m.73A&gt;G (OR: 0.46, 95% CI: 0.28–0.77, <i>p</i> = 0.003), m.185G&gt;A (OR: 0.41, 95% CI: 0.18–0.92, <i>p</i> = 0.030), m.16051A&gt;G (OR: 0.24, 95% CI: 0.07–0.84, <i>p</i> = 0.026), m.16092T&gt;A (OR: 9.21, 95% CI: 1.11–76.42, <i>p</i> = 0.040) and m.16291C&gt;T (OR: 2.35, 95% CI: 1.29–4.28, <i>p</i> = 0.005) in the D-loop region and m.6228C&gt;T (OR: 9.41, 95% CI: 1.14–77.59, <i>p</i> = 0.037) in <i>MT-CO1</i> gene were found to be significantly different between GDM cases and the controls.</p> Conclusions <p>This study revealed an association between mtDNA variations and GDM, highlighting the potential that screening for specific mtDNA variants in early pregnancy may predict the development of GDM.</p>

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Mitochondrial DNA variations and risk of incident gestational diabetes mellitus: a nested case-control study

  • 期刊论文

  • 发表日期：

    2025年6月20日

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  • Yuqing Liu,
  • Xiao Li,
  • Maoning Zhao,
  • Yun Zhao,
  • Yuanzhong Zhou,
  • Hongsong Yu,
  • Kai Zhao,
  • Shigang Zhao,
  • Xuejun Shang

摘要

Aims

Gestational diabetes mellitus (GDM) is associated with mitochondrial dysfunction. Mitochondrial DNA (mtDNA) plays a critical role in mitochondrial function, affecting cellular oxidative phosphorylation and ATP supply. This study aims to explore the association between mtDNA variations and GDM in Han Chinese women.

Methods

This nested case-control study was conducted among 701 women who developed GDM and 859 contemporaneous controls based on the Chinese Birth Cohort of Environmental and Genetic Factors between 2018 and 2022. Next-generation sequencing was performed on the samples to detect variations in the whole mitochondrial genome. The sequencing data were analyzed, and the differences in the number of mtDNA variations between the two groups were assessed using a t-test. Haplogroup analysis was conducted through the chi-square test. Logistic regression analysis was performed, adjusting for age, BMI, gravidity, and parity, to identify significantly different mtDNA variations between the two groups.

Results

Pregnant women with GDM carried fewer mtDNA variants in the D-loop region (11.35 ± 2.77 vs. 11.80 ± 2.86, p = 0.002). Results indicated that m.73A>G (OR: 0.46, 95% CI: 0.28–0.77, p = 0.003), m.185G>A (OR: 0.41, 95% CI: 0.18–0.92, p = 0.030), m.16051A>G (OR: 0.24, 95% CI: 0.07–0.84, p = 0.026), m.16092T>A (OR: 9.21, 95% CI: 1.11–76.42, p = 0.040) and m.16291C>T (OR: 2.35, 95% CI: 1.29–4.28, p = 0.005) in the D-loop region and m.6228C>T (OR: 9.41, 95% CI: 1.14–77.59, p = 0.037) in MT-CO1 gene were found to be significantly different between GDM cases and the controls.

Conclusions

This study revealed an association between mtDNA variations and GDM, highlighting the potential that screening for specific mtDNA variants in early pregnancy may predict the development of GDM.