Abstract
Background
The level and lactonase activity of paraoxonase 1 (PON1) and their association with PON1 genetic variants and oxidative stress are unclear in neonates of women with gestational diabetes mellitus (GDM).
Methods
This study included 362 neonates of women with GDM and 302 control neonates. The level, lactonase activity, normalized lactonase activity (NLA), and genetic polymorphisms of PON1, serum total oxidant status (TOS), total antioxidant capacity (TAC), and malondialdehyde (MDA) were analyzed.
Results
The neonates of the women with GDM had significantly higher levels, lactonase activity, and NLA of PON1, higher TOS, TAC, and MDA concentrations, and relatively higher oxidative stress index than those of the control neonates. The PON1 −108C → T variation decreased the lactonase activity, level, and NLA of PON1, while the PON1 192Q → R variation decreased the PON1 NLA in a genotype-dependent manner in the two groups. Multivariable regression analysis revealed the PON1 −108C/T or 192Q/R variation, apolipoprotein (apo)A1, or apoB as significant predictors of the level, lactonase activity, and NLA of PON1.
Conclusions
The lactonase activity, level, and NLA of PON1 were increased in the neonates of women with GDM. The PON1 genetic variants, abnormalities in lipoproteins, and increased oxidative stress may be associated with these changes.
Impact
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This is the first study to report the elevated level, lactonase activity, and NLA of PON1 in the neonates of women with GDM.
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These neonates also exhibited increased oxidative stress and an adverse glycolipid metabolic profile.
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We further established that the −108C/T and/or 192Q/R genetic variants of the PON1 gene, abnormalities in lipoprotein metabolism, and/or increased oxidative stress had noticeable influences on the level and activities of PON1.
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Whether these changes potentially cause metabolic disorders later in life remains to be determined. Therefore, the neonates born to women with GDM require further clinical follow-ups.
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Acknowledgements
We thank the women with GDM and the control group women who donated cord blood samples for this study. We also appreciate Qian Gao for participating in the sample collection. This study was supported by the Key Research and Development Project of Sichuan Province (grant no. 2019YFS0401), the National Key Research and Development Program of China (grant no. 2016YFC1000400) and the Program for Changjiang Scholars and Innovative Research Team in University, Ministry of Education (grant no. IRT0935).
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M.Z. collected samples, conducted experiments, and wrote the paper. P.F. designed the experiments, analyzed the data, and revised the paper. X.-H.L. and M.C. were responsible for patient screening and helped with the sample collection. Q.-Q.L., C.-Y.J., and L.-B.G. assisted with the experiments. H.B. helped with the data analysis of the results and revised the paper. All authors read and approved the final manuscript to be published.
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The present study was approved by the Institutional Review Board of the West China Second University Hospital, Sichuan University. All subjects provided their written informed consent in accordance with the Helsinki Declaration of ethical conduct in research.
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Zhou, M., Liu, XH., Liu, QQ. et al. Lactonase activity and status of paraoxonase 1 and oxidative stress in neonates of women with gestational diabetes mellitus. Pediatr Res 89, 1192–1199 (2021). https://doi.org/10.1038/s41390-020-1023-2
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DOI: https://doi.org/10.1038/s41390-020-1023-2
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