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Nutrition during the early life cycle

Association of polymorphisms of FOLR1 gene and FOLR2 gene and maternal folic acid supplementation with risk of ventricular septal defect: a case-control study

European Journal of Clinical Nutrition volume 76, pages 1273–1280 (2022)Cite this article

Subjects

Abstract

Objectives

It was the first time to examine the role of maternal polymorphisms of FOLR1 gene and FOLR2 gene, as well as their interactions with maternal folic acid supplementation (FAS), in the risk of ventricular septal defect (VSD).

Methods

A case-control study was conducted with 385 mothers of VSD infants and 652 controls. The exposures of interest were FAS and FOLR1 gene and FOLR2 gene polymorphisms. The logistic regression model was used for accessing the strength of association.

Results

After controlling for the potential confounders, women who did not utilize folic acid had a substantially higher risk of VSD (aOR = 2.25; 95% CI: 1.48 to 3.43), compared to those who did. We also observed genetic polymorphisms of FOLR1 gene at rs2071010 (GA vs. GG: aOR = 0.63, 95%CI: 0.45 to 0.88) and rs11235462 (AA vs. TT: aOR = 0.53, 95%CI: 0.33 to 0.84), as well as FOLR2 gene at rs651646 (AA vs. TT: aOR = 0.46, 95%CI: 0.30 to 0.70), rs2298444 (CC vs. TT: aOR = 0.58, 95%CI: 0.36 to 0.91) and rs514933 (TC vs. TT: aOR = 0.57, 95%CI: 0.41 to 0.78) were associated with a lower risk of VSD. Furthermore, there was a statistically significant interaction between maternal FAS and genetic polymorphisms at rs514933 on the risk of VSD (FDR_P = 0.015).

Conclusions

The maternal genetic polymorphisms of the FOLR1 gene and FOLR2 gene, as well as FAS and their interactions, were shown to be significantly associated with the risk of VSD in offspring.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to thank the editors and reviewers for their suggestions and all colleagues working in Maternal and Child Health Promotion and Birth Defect Prevention Group.

Funding

This study was supported by the Project Funded by National Natural Science Foundation Program of China (82073653 and 81803313), Hunan Provincial Key Research and Development Program (2018SK2063 and 2018SK2062), Hunan Provincial Science and Technology Talent Support Project (2020TJ-N07), Natural Science Foundation of Hunan Province (2018JJ2551), Open Project from NHC Key Laboratory of Birth Defect for Research and Prevention (KF2020006), and The 68th General Program Supported by China Postdoctoral Science Foundation (2020M682644).

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Authors and Affiliations

  1. Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, China

    Xinli Song, Jianhui Wei, Jing Shu, Yiping Liu, Mengting Sun & Jiabi Qin

  2. Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China

    Ping Zhu & Jiabi Qin

  3. NHC Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, China

    Jiabi Qin

  4. Hunan Provincial Key Laboratory of clinical epidemiology, Changsha, Hunan, China

    Jiabi Qin

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Contributions

Conceived and designed the experiments: PZ, JBQ, XLS and JHW. Performed the experiments: MTS and YPL. Analyzed the data and statistical analyses: JS and MTS. Contributed reagents/material/analysis tools: JS, YPL and MTS. Wrote the main manuscript text: XLS and PZ. Reference collection and data management: JBQ and XLS. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Ping Zhu or Jiabi Qin.

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Song, X., Wei, J., Shu, J. et al. Association of polymorphisms of FOLR1 gene and FOLR2 gene and maternal folic acid supplementation with risk of ventricular septal defect: a case-control study. Eur J Clin Nutr 76, 1273–1280 (2022). https://doi.org/10.1038/s41430-022-01110-9

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