Dataset Information

Association of MTHFD1 gene polymorphisms and maternal smoking with risk of congenital heart disease: a hospital-based case-control study.

ABSTRACT:

Background

MTHFD1 gene may affect the embryonic development by elevated homocysteine levels, DNA synthesis and DNA methylation, but limited number of genetic variants of MTHFD1 gene was focused on the association with congenital heart disease (CHD). This study examined the role of MTHFD1 gene and maternal smoking on infant CHD risk, and investigated their interaction effects in Chinese populations.

Methods

A case-control study of 464 mothers of CHD infants and 504 mothers of health controls was performed. The exposures of interest were maternal tobacco exposure, single nucleotide polymorphisms (SNPs) of maternal MTHFD1 gene. The logistic regression model was used for accessing the strength of association.

Results

Mothers exposed to secondhand smoke during 3 months before pregnancy (adjusted odds ratio [aOR] = 1.56; 95% confidence interval [CI]: 1.13-2.15) and in the first trimester of pregnancy (aOR = 2.24; 95%CI: 1.57-3.20) were observed an increased risk of CHD. Our study also found that polymorphisms of maternal MTHFD1 gene at rs1950902 (AA vs. GG: aOR = 1.73, 95% CI: 1.01-2.97), rs2236222 (GG vs. AA: aOR = 2.38, 95% CI: 1.38-4.12), rs1256142 (GA vs.GG: aOR = 1.57, 95% CI: 1.01-2.45) and rs11849530 (GG vs. AA: aOR = 1.68, 95% CI: 1.02-2.77) were significantly associated with higher risk of CHD. However, we did not observe a significant association between maternal MTHFD1 rs2236225 and offspring CHD risk. Furthermore, we found the different degrees of interaction effects between polymorphisms of the MTHFD1 gene including rs1950902, rs2236222, rs1256142, rs11849530 and rs2236225, and maternal tobacco exposure.

Conclusions

Maternal polymorphisms of MTHFD1 gene, maternal tobacco exposure and their interactions are significantly associated with the risk of CHD in offspring in Han Chinese populations. However, more studies in different ethnic populations with a larger sample and prospective designs are required to confirm our findings.

Trial registration

Registration number: ChiCTR1800016635 .

SUBMITTER: Song X

PROVIDER: S-EPMC8805321 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Publications

Association of MTHFD1 gene polymorphisms and maternal smoking with risk of congenital heart disease: a hospital-based case-control study.

Song Xinli X Li Qiongxuan Q Diao Jingyi J Li Jinqi J Li Yihuan Y Zhang Senmao S Zhao Lijuan L Chen Letao L Wei Jianhui J Shu Jing J Liu Yiping Y Sun Mengting M Huang Peng P Wang Tingting T Qin Jiabi J

BMC pregnancy and childbirth 20220131 1

<h4>Background</h4>MTHFD1 gene may affect the embryonic development by elevated homocysteine levels, DNA synthesis and DNA methylation, but limited number of genetic variants of MTHFD1 gene was focused on the association with congenital heart disease (CHD). This study examined the role of MTHFD1 gene and maternal smoking on infant CHD risk, and investigated their interaction effects in Chinese populations.<h4>Methods</h4>A case-control study of 464 mothers of CHD infants and 504 mothers of healt ...[more]

PMID: 35100977

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Project description:ObjectivesTo study the association of maternal methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) gene polymorphisms with congenital heart disease (CHD) in offspring.MethodsA hospital-based case-control study was conducted. The mothers of 683 children with CHD alone who attended Hunan Children's Hospital, from November 2017 to March 2020 were enrolled as the case group, and the mothers of 740 healthy children who attended the same hospital during the same period and did not have any deformity were enrolled as the control group. A questionnaire survey was performed to collect related exposure data, and then venous blood samples (5 mL) were collected from the mothers to detect MTHFD1 and MTHFD2 gene polymorphisms. A multivariate logistic regression analysis was used to evaluate the association of MTHFD1 and MTHFD2 gene polymorphisms with CHD. The four-gamete test in Haploview 4.2 software was used to construct haplotypes and evaluate the association between haplotypes and CHD. The generalized multifactor dimensionality reduction method and logistic regression analysis were used to examine gene-gene interaction and its association with CHD.ResultsThe multivariate logistic regression analysis showed that maternal MTHFD1 gene polymorphisms at rs11849530 (GA vs AA: OR=1.49; GG vs AA: OR=2.04) andat rs1256142 (GA vs GG: OR=2.34; AA vs GG: OR=3.25) significantly increased the risk of CHD in offspring (P<0.05), while maternal MTHFD1 gene polymorphisms at rs1950902 (AA vs GG: OR=0.57) and MTHFD2 gene polymorphisms at rs1095966 (CA vs CC: OR=0.68) significantly reduced the risk of CHD in offspring (P<0.05). The haplotypes of G-G-G (OR=1.86) and G-A-G (OR=1.35) in mothers significantly increased the risk of CHD in offspring (P<0.05). The gene-gene interaction analyses showed that the first-order interaction between MTHFD1 rs1950902 and MTHFD1 rs2236222 and the second-order interaction involving MTHFD1 rs1950902, MTHFD1 rs1256142, and MTHFD2 rs1095966 might be associated with risk of CHD (P<0.05).ConclusionsMaternal MTHFD1 and MTHFD2 gene polymorphisms and their haplotypes, as well as the interaction between MTHFD1 rs1950902 and MTHFD1 rs2236222 and between MTHFD1 rs1950902, MTHFD1 rs1256142, and MTHFD2 rs1095966, are associated with the risk of CHD in offspring.

Project description:BackgroundThe 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.MethodsA 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.ResultsThere 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.ConclusionsThe 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.

Project description:ObjectivesThis study aimed at assessing the association between maternal methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) gene polymorphisms, maternal dietary habits, and their interactions with the risk of ventricular septal defects (VSD) in offspring.MethodsFrom November 2017 to March 2019, a case-control study comprising 360 mothers of VSD cases and 504 mothers of healthy infants was conducted in Han Chinese populations. The main exposures of interest were maternal dietary habits in early pregnancy and MTHFD1 gene polymorphisms. Logistic regression models were used to estimate the main effects and interaction effects.ResultsIt was observed that maternal excessive intake of pickled vegetables (aOR = 1.85, 95%CI: 1.45-2.37), smoked foods (aOR = 1.93, 95%CI: 1.48-2.51), barbecued foods (aOR = 1.74, 95%CI: 1.28-2.36), and fried foods (aOR = 1.68, 95%CI: 1.30-2.17) were associated with a higher risk of VSD in offspring, whereas maternal excessive intake of fresh meat (aOR = 0.61, 95%CI: 0.47-0.79), fish and shrimp (aOR = 0.29, 95%CI: 0.23-0.38), fresh eggs (aOR = 0.54, 95%CI: 0.42-0.70), fresh fruits or vegetables (aOR = 0.44, 95%CI: 0.33-0.60), soy foods (aOR = 0.65, 95%CI: 0.53-0.80), and milk products (aOR = 0.49, 95%CI: 0.40-0.59) could contribute significantly to a lower risk of VSD in offspring. Furthermore, the genetic polymorphisms of maternal MTHFD1 gene at rs1950902 (GA vs. GG: aOR = 0.67, 95%CI: 0.50-0.90) and rs2236222 (GG vs. AA: aOR = 2.75, 95%CI: 1.57-4.83) were significantly associated with the risk of VSD in offspring. In addition, there was a significant interaction effect between maternal dietary habits and MTHFD1 gene polymorphisms on the risk of VSD.ConclusionsMaternal dietary factors, MTHFD1 genetic polymorphisms, and their interactions were all associated with the risk of VSD in offspring. However, further research in diverse ethnic populations and with a larger sample size is warranted to corroborate our findings.Trial registrationRegistered in Chinese Clinical Trial Registry Center; registration number, ChiCTR1800016635; registration date, 06/14/2018 (Retrospectively registered); URL of trial registry record, https://www.chictr.org.cn/showproj.aspx?proj=28300.

Project description:BackgroundAlthough many studies shown that the risk of congenital heart disease (CHD) was closely related to genetic and environmental factors, the exact mechanism was still unclear. This study was to assess the association of maternal folic acid supplementation (FAS), the 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) gene polymorphisms in offspring and their interaction effects with the risk of CHD and its subtypes.MethodsA case-control study was conducted on 595 children with CHD and 605 healthy child controls. The multivariate logistic regression model was used to assess the association of maternal FAS, offspring MTRR gene polymorphisms and their interaction effects with CHD and its subtypes.ResultsThis study shown that maternal FAS was significantly associated with a reduced risk of CHD (OR = 0.55, 95%CI: 0.36-0.83) and its subtypes including ASD (OR = 0.25, 95%CI: 0.14-0.45), VSD (OR = 0.42, 95%CI: 0.27-0.64), and CTD (OR = 0.23, 95%CI: 0.09-0.59) in offspring. Offspring MTRR gene polymorphisms at rs162048 (GG vs. AA: OR = 2.05, 95%CI: 1.35-3.13), rs1802059 (AA vs. GG: OR = 5.13, 95%CI: 2.15-12.23; GA vs. GG: OR = 1.81, 95%CI: 1.35-2.43), rs10380 (TT vs. CC: OR = 2.27, 95%CI: 1.20-4.31) and rs1801394 (GG vs. AA: OR = 1.58, 95%CI: 1.02-2.42) were significantly associated with the risk of CHD, and similar results were also found for three subtypes of CHD. Additionally, a statistically significant interaction effect between maternal FAS and offspring MTRR gene polymorphism at rs1802059 was observed (OR = 0.38, 95%CI: 0.15-0.94). Among children who had a variant genotype at rs1802059, the risk of CHD was significantly decreased when their mother used folate for this pregnancy compared with mothers not using folate.ConclusionsIn those of Chinese descent, maternal FAS and offspring MTRR gene polymorphisms are significantly associated with the risk of CHD and its three subtypes. Furthermore, maternal FAS may help to offset some of risks of CHD due to offspring MTRR genetic variants. However, more studies with prospective designs and larger samples are needed to confirm our findings.Trial registrationRegistration number: ChiCTR1800016635; Registration time: 14/06/2018.

Dataset Information

Association of MTHFD1 gene polymorphisms and maternal smoking with risk of congenital heart disease: a hospital-based case-control study.

Background

Methods

Results

Conclusions

Trial registration

Publications

Association of MTHFD1 gene polymorphisms and maternal smoking with risk of congenital heart disease: a hospital-based case-control study.

Similar Datasets

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