Mitochondrial DNA content and deletion ratio are associated with metabolic syndrome in a general population exposed to pesticide

Abstract

Background

Mitochondrial DNA (mtDNA) copy number and deletion ratio may be asymmetrically determined using physiologic or pathologic conditions. Mitochondrial dysfunction is associated with an increased risk of developing metabolic syndrome (MetS).

Objective

Here, we investigated the association between mtDNA copy number and/or deletion ratio and the risk of developing MetS in a general population exposed to the pesticide. We examined 215 randomly sampled adults who were exposed to pesticide but did not present with MetS in a prospective cohort study. Both mtDNA copy number and deletion ratio were determined using quantitative real-time polymerase chain reaction.

Results

During the average 2.8-year follow-up period, 76 (35.3%) participants developed new-onset MetS. The numbers of mtDNA copies were significantly lower in participants with new-onset MetS than in those without MetS (112.15 ± 26.15 vs. 133.13 ± 44.44, p < 0.001), whereas the mtDNA deletion ratios were higher in participants with MetS than in those without MetS (10.59 ± 11.96 vs. 4.52 ± 6.74, p < 0.001). In the multivariate-adjusted models, the participants with a higher tertile of mtDNA copy number were 0.355 times more likely to develop MetS than those with the lowest tertile [odds ratio (OR) 0.355, 95% confidence interval (CI) 0.150–0.841, p = 0.004]. A higher mtDNA deletion ratio was significantly associated with the risk of developing MetS in populations exposed to pesticide (OR 5.062, 95% CI 1.164–22.004, p = 0.004).

Conclusion

A lower mtDNA copy number and higher deletion ratio were independent predictors for new-onset MetS in a general population exposed to the pesticide.

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Fig. 1

Data availability

The datasets generated and/or analyzed during the current study are available in the Korea National Institute of Health (KNIH) repository (https://www.nih.go.kr/NIH_NEW/main.jsp).

Abbreviations

mtDNA:

Mitochondrial DNA

MetS:

Metabolic syndrome

OR:

Odds ratio

CI:

Confidence interval

T2DM:

Type 2 diabetes mellitus

KoGES-ARIRANG:

Korean Genome and Epidemiology Study on the Atherosclerosis Risk of Rural Areas in the Korean General Population

WC:

Waist circumference

SBP:

Systolic blood pressure

DBP:

Diastolic blood pressure

LDL:

Low-density lipoprotein

HDL:

High-density lipoprotein

TG:

Triglyceride

HOMA-IR:

Homeostasis model assessment of insulin resistance

qPCR:

Quantitative polymerase chain reaction

mtMinArc:

Mitochondrial minor arc

mtMajArc:

Mitochondrial major arc

ND4:

NADH dehydrogenase subunit 4

BMI:

Body mass index

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Funding

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (2017R1D1A3B03034119). Moreover, this research was supported by the Medical Research Center Program 2017R1A5A2015369. This work was carried out with the support of the Cooperative Research Program for Agriculture Science & Technology Development (project no.: PJ01250901) Rural Development Administration, Republic of Korea. This work was supported (in part) by the Yonsei University Research Fund of 2017.

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All authors are responsible for the design of the work. JRC and SBK performed the data analysis and drafted the manuscript. SP, SK, JK, KL and SSO provided a critical review of the data analysis and manuscript. 'All authors read and approved the final manuscript' All authors read and approved for the final manuscript.

Corresponding authors

Correspondence to Jung Ran Choi or Sang Baek Koh.

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Ethical approval

This study was included human participants and human data, a statement on ethics approval and consent, and the name of the ethics committee that approved the study. This study was approved by the Institutional Review Board of the Wonju Christian Hospital, according to the Helsinki Declaration. All the participants provided informed written consent.

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Choi, J.R., Park, S., Kim, S. et al. Mitochondrial DNA content and deletion ratio are associated with metabolic syndrome in a general population exposed to pesticide. Mol. Cell. Toxicol. 16, 347–354 (2020). https://doi.org/10.1007/s13273-020-00079-5

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Keywords

  • mtDNA copy number
  • Deletion ratio
  • Metabolic syndrome
  • Pesticide exposure