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The neonatal PROC gene rs1799809 polymorphism modifies the association between prenatal air pollutants exposure and PROC promoter methylation

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Abstract

Prenatal air pollution, protein C (PROC) gene abnormal methylation, and genetic mutation can cause a series of neonatal diseases, but the complex relationship between them remains unclear. Here, we recruited 552 mothers and their own babies during January 2010–January 2012 in Zhengzhou to explore such association. The air pollutant data was obtained from the Environmental Monitoring Stations. The rs1799809 genotype and the methylation levels at the promoter region of PROC in genomic DNA samples were detected respectively by TaqMan probe and quantitative methylation specific PCR using real-time PCR system. The results show that the levels of neonatal PROC methylation were negatively associated with concentrations of NO2 during the entire pregnancy, particularly during the third trimester. Of particular significance, only in newborns carrying rs1799809 AA genotype, negatively significant associations between PROC methylation levels and exposure concentrations of air pollutants were observed. Further, we observed a significant interactive effect between neonatal rs1799809 genotype and SO2 exposure during the entire pregnancy on neonatal PROC methylation levels. Prenatal exposure to ambient air pollutants specifically was associated with the neonatal PROC promoter methylation level of newborns carrying the rs1799809 AA genotype. Taken together, these findings suggest that neonatal PROC methylation levels are associated with prenatal exposure to ambient air pollutants, and this association can be modified by rs1799809 genotype.

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Acknowledgements

We would like to express our gratitude to the members of the Houzhai Health Hospital and all the subjected investigated for their consent, help, and support. This study was supported by the National Natural Science Foundation of China, and the Opening Foundation of National Health Commission Key Laboratory of Birth Defects Prevention and Henan Key Laboratory of Population Defects Prevention. The sponsors were not involved in study design, information collection, data analysis, report writing, and publication.

Availability of data and materials

The datasets generated during and/or analyzed during the current study are not publicly available due to the sensitivity of human data but are available from the corresponding author on reasonable request.

Funding

This study was supported by the National Natural Science Foundation of China (82003401 and 81972981 and 81673116), and the Opening Foundation of National Health Commission Key Laboratory of Birth Defects Prevention and Henan Key Laboratory of Population Defects Prevention (ZD202001).

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Authors and Affiliations

  1. Department of Environmental Health, School of Public Health, Zhengzhou University, 100 Science Avenue, Zhengzhou, Henan, 450001, People’s Republic of China

    Zhiyuan Li, Meng Yang, Leizhen Duan, Yongxiang Gong, Hongxia Xia, Francis-Kojo Afrim, Hui Huang, Xiaoxue Liu, Fangfang Yu, Yue Ba & Guoyu Zhou

  2. Department of Environment Health Science, Yale University School of Public Health, New Haven, CT, USA

    Yawei Zhang

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  1. Zhiyuan Li
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Contributions

Zhiyuan Li: conceptualization, investigation, writing—original draft. Meng Yang: writing—original draft; visualization. Leizhen Duan: methodology, formal analysis, visualization. Yongxiang Gong: visualization, writing—review and editing. Hongxia Xia: validation, writing—review and editing. Francis-Kojo Afrim: validation, writing—review and editing. Hui Huang: investigation, writing—review and editing. Xiaoxue Liu: resources, writing—review and editing. Fangfang Yu: data curation, writing—review and editing. Yawei Zhang: writing—review and editing. Yue Ba: conceptualization; supervision; funding acquisition; writing—review and editing. Guoyu Zhou: methodology; conceptualization; project administration; funding acquisition; writing—review and editing.

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Correspondence to Guoyu Zhou.

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This study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study design was approved by the Ethics Committee of Zhengzhou University. And the private information was de-identified to protect the privacy of participants.

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Li, Z., Yang, M., Duan, L. et al. The neonatal PROC gene rs1799809 polymorphism modifies the association between prenatal air pollutants exposure and PROC promoter methylation. Environ Sci Pollut Res 29, 14575–14583 (2022). https://doi.org/10.1007/s11356-021-16694-1

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