Association of maternal phthalates exposure and metabolic gene polymorphisms with congenital heart diseases: a multicenter case-control study
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 w...
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | BMC Pregnancy and Childbirth |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12884-024-06343-z |
| _version_ | 1797272908664406016 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Nana Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T14:36:03Z |
| format | Article |
| id | doaj.art-94266d1a60cb43a080fb956dfa0e6641 |
| institution | Directory Open Access Journal |
| issn | 1471-2393 |
| language | English |
| last_indexed | 2024-03-07T14:36:03Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Pregnancy and Childbirth |
| spelling | doaj.art-94266d1a60cb43a080fb956dfa0e66412024-03-05T20:39:42ZengBMCBMC Pregnancy and Childbirth1471-23932024-02-0124111210.1186/s12884-024-06343-zAssociation of maternal phthalates exposure and metabolic gene polymorphisms with congenital heart diseases: a multicenter case-control studyNana Li0Hong Kang1Zhen Liu2Lu Li3Ying Deng4Meixian Wang5Yuting Li6Wenli Xu7Xiaohong Li8Yanping Wang9Jun Zhu10Jing Tao11Ping Yu12National Center for Birth Defect Monitoring, West China Second University Hospital, Sichuan UniversityNational Center for Birth Defect Monitoring, West China Second University Hospital, Sichuan UniversityNational Center for Birth Defect Monitoring, West China Second University Hospital, Sichuan UniversityNational Center for Birth Defect Monitoring, West China Second University Hospital, Sichuan UniversityNational Center for Birth Defect Monitoring, West China Second University Hospital, Sichuan UniversityNational Center for Birth Defect Monitoring, West China Second University Hospital, Sichuan UniversityNational Center for Birth Defect Monitoring, West China Second University Hospital, Sichuan UniversityDepartment of Maternal Healthcare, Pidu Maternal and Child Care HospitalNational Center for Birth Defect Monitoring, West China Second University Hospital, Sichuan UniversityNational Center for Birth Defect Monitoring, West China Second University Hospital, Sichuan UniversityNational Center for Birth Defect Monitoring, West China Second University Hospital, Sichuan UniversityNational Center for Birth Defect Monitoring, West China Second University Hospital, Sichuan UniversityNational Center for Birth Defect Monitoring, West China Second University Hospital, Sichuan UniversityAbstract 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.https://doi.org/10.1186/s12884-024-06343-zCongenital heart diseasesPhthalatesUridine diphosphate (UDP) glucuronosyl transferase family 1 member A7 (UGT1A7)Interaction |
| spellingShingle | 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 Association of maternal phthalates exposure and metabolic gene polymorphisms with congenital heart diseases: a multicenter case-control study BMC Pregnancy and Childbirth Congenital heart diseases Phthalates Uridine diphosphate (UDP) glucuronosyl transferase family 1 member A7 (UGT1A7) Interaction |
| title | Association of maternal phthalates exposure and metabolic gene polymorphisms with congenital heart diseases: a multicenter case-control study |
| title_full | Association of maternal phthalates exposure and metabolic gene polymorphisms with congenital heart diseases: a multicenter case-control study |
| title_fullStr | Association of maternal phthalates exposure and metabolic gene polymorphisms with congenital heart diseases: a multicenter case-control study |
| title_full_unstemmed | Association of maternal phthalates exposure and metabolic gene polymorphisms with congenital heart diseases: a multicenter case-control study |
| title_short | Association of maternal phthalates exposure and metabolic gene polymorphisms with congenital heart diseases: a multicenter case-control study |
| title_sort | association of maternal phthalates exposure and metabolic gene polymorphisms with congenital heart diseases a multicenter case control study |
| topic | Congenital heart diseases Phthalates Uridine diphosphate (UDP) glucuronosyl transferase family 1 member A7 (UGT1A7) Interaction |
| url | https://doi.org/10.1186/s12884-024-06343-z |
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