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BMC Pregnancy and Childbirth
Published in: BMC Pregnancy and Childbirth 1/2024

Open Access 01-12-2024 | Research

Association of maternal phthalates exposure and metabolic gene polymorphisms with congenital heart diseases: a multicenter case-control study

Authors: Nana Li, Hong Kang, Zhen Liu, Lu Li, Ying Deng, Meixian Wang, Yuting Li, Wenli Xu, Xiaohong Li, Yanping Wang, Jun Zhu, Jing Tao, Ping Yu

Published in: BMC Pregnancy and Childbirth | Issue 1/2024

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Abstract

Background

The majority of congenital heart diseases (CHDs) are thought to result from the interactions of genetics and the environment factors. This study aimed to assess the association of maternal non-occupational phthalates exposure, metabolic gene polymorphisms and their interactions with risk of CHDs in offspring.

Methods

A multicenter case-control study of 245 mothers with CHDs infants and 268 control mothers of health infant was conducted from six hospitals. Maternal urinary concentrations of eight phthalate metabolites were measured by ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Twenty single nucleotide polymorphisms (SNPs) in cytochrome P450 family 2 subfamily C member 9 (CYP2C9) and 19 (CYP2C19), uridine diphosphate (UDP) glucuronosyl transferase family 1 member A7 (UGT1A7), family 2 member B7 (UGT2B7) and B15(UGT2B15) genes were genotyped. The multivariate logistic regressions were used to estimate the association between maternal phthalates exposure or gene polymorphisms and risk of CHDs. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene–gene and gene–phthalates exposure interactions.

Results

There was no significant difference in phthalate metabolites concentrations between the cases and controls. No significant positive associations were observed between maternal exposure to phthalates and CHDs. The SNPs of UGT1A7 gene at rs4124874 (under three models, log-additive: aOR = 1.74, 95% CI:1.28–2.37; dominant: aOR = 1.86, 95% CI:1.25–2.78; recessive: aOR = 2.50, 95% CI: 1.26–4.94) and rs887829 (under the recessive model: aOR = 13.66, 95% CI: 1.54–121) were significantly associated with an increased risk of CHDs. Furthermore, the associations between rs4124874 (under log-additive and dominant models) of UGT1A7 were statistically significant after the false discovery rate correction. No significant gene-gene or gene-phthalate metabolites interactions were observed.

Conclusions

The polymorphisms of maternal UGT1A7 gene at rs4124874 and rs887829 were significantly associated with an increased risk of CHDs. More large-scale studies or prospective study designs are needed to confirm or refute our findings in the future.
Appendix
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Metadata
Title
Association of maternal phthalates exposure and metabolic gene polymorphisms with congenital heart diseases: a multicenter case-control study
Authors
Nana Li
Hong Kang
Zhen Liu
Lu Li
Ying Deng
Meixian Wang
Yuting Li
Wenli Xu
Xiaohong Li
Yanping Wang
Jun Zhu
Jing Tao
Ping Yu
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Pregnancy and Childbirth / Issue 1/2024
Electronic ISSN: 1471-2393
DOI
https://doi.org/10.1186/s12884-024-06343-z

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