Dataset Information

Association of methylenetetrahydrofolate reductase gene polymorphisms and maternal folic acid use with the risk of congenital heart disease.

ABSTRACT:

Background

To systematically evaluate the association of MTHFR genetic polymorphisms, maternal folic acid intake, and the time when folic acid intake was started with the risk of congenital heart disease (CHD) and investigated the role of their interaction on infant CHD risk in Chinese populations.

Methods

A case-control study involving 592 CHD cases, 617 health controls, and their mothers was performed. The exposures of interest were single nucleotide polymorphisms (SNPs) of the MTHFR gene, maternal folic acid use, and the time when folic acid use was started. We applied the logistic regression model to explore the strength of association.

Results

Our findings showed that mothers lacking folic acid intake had a significantly higher risk of CHD in offspring (aOR = 2.00; 95%CI: 1.34-2.98). Mothers who started to use folic acid from the first trimester of the fetation (aOR = 1.65; 95% CI: 1.22-2.23) or from the second trimester of the fetation (aOR = 7.77; 95% CI: 2.52-23.96), compared with those starting to use folic acid from 3 months previous to the conception, were at a significantly higher risk of CHD in offspring. Genetic variants at rs2066470 (AA vs. GG: aOR = 5.09, 95%CI: 1.99-13.03), rs1801133 (AA vs. GG: aOR = 2.49, 95%CI: 1.58-3.93), and rs1801131 (TG vs. TT: aOR = 1.84, 95%CI: 1.36-2.50; GG vs. TT: aOR = 3.58, 95%CI: 1.68-7.63) were significantly associated with the risk of CHD based on the multivariate analysis. Additionally, statistically significant interactions between maternal folic acid intake and genetic variants of the MTHFR gene at rs1801133 and rs1801131 were observed.

Conclusion

An association of maternal folic acid intake and the time when intake was started with the risk of CHD in offspring was found. What's more, maternal folic acid fortification may help counteract partial of the risks of CHD in offspring attributable to MTHFR genetic mutations.

Registration number

http://www.chictr.org.cn/edit.aspx?pid=28300&htm=4, identifier: ChiCTR1800016635.

SUBMITTER: Zhong T

PROVIDER: S-EPMC9492935 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Association of methylenetetrahydrofolate reductase gene polymorphisms and maternal folic acid use with the risk of congenital heart disease.

Zhong Taowei T Song Xinli X Liu Yiping Y Sun Mengting M Zhang Senmao S Chen Letao L Diao Jingyi J Li Jinqi J Li Yihuan Y Shu Jing J Wei Jianhui J Zhu Ping P Wang Tingting T Qin Jiabi J

Frontiers in pediatrics 20220908

<h4>Background</h4>To systematically evaluate the association of <i>MTHFR</i> genetic polymorphisms, maternal folic acid intake, and the time when folic acid intake was started with the risk of congenital heart disease (CHD) and investigated the role of their interaction on infant CHD risk in Chinese populations.<h4>Methods</h4>A case-control study involving 592 CHD cases, 617 health controls, and their mothers was performed. The exposures of interest were single nucleotide polymorphisms (SNPs) ...[more]

PMID: 36160803

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Project description:BackgroundCongenital heart disease (CHD), which involve congenital cardiovascular malformations that occur during an embryo stage, may be the result of a complex interaction between genetic factors and environmental factors. The homozygous 677 T/T MTHFR gene and potential factors have been associated with CHD. Our objective was to study associations between potential environmental risk factors and methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms in CHD.MethodsA total of 346 children with CHD and 237 healthy children were recruited. Their parents were also enlisted in the study and interviewed face-to-face to identify potential environmental risk factors. The MTHFR genotype was analyzed by restriction fragment length polymorphism (RFLP). Interactions between environmental risk factors and MTHFR gene polymorphisms were evaluated by the relative excess risk due to interaction (RERI), the attributable proportion due to interaction (AP), and the synergy index (S).ResultsThere were significant differences in the occupational statuses of the mothers and their levels of drug exposure during gestation between the controls and the cases (P<0.05). These differences significantly increased offspring CHD risk (occupation: OR =5.45, 95% CI: 3.46-8.58; drug exposure: OR =4.91, 95% CI: 2.18-11.09). The frequency of the MTHFR gene 677 TT polymorphism in the mothers who had offspring with CHD was significantly different from that in the non-CHD controls (P<0.05). The frequency of this polymorphism also significantly differed between the children with CHD and the control group (P<0.05). An interaction was identified between the presence of the homozygous 677 TT genotype in the children and the mothers' occupational statuses (RERI =9.43, CI: 0.06-18.91).ConclusionsA significant interaction was found between the homozygous 677 T/T MTHFR gene in children and the maternal occupational status and level of drug exposure during gestation. Avoiding or reducing the exposure of the risk factors mentioned above, strengthening pre-pregnancy checkups and guidance might help to reduce the risk of CHD.

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.

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Dataset Information

Association of methylenetetrahydrofolate reductase gene polymorphisms and maternal folic acid use with the risk of congenital heart disease.

Background

Methods

Results

Conclusion

Registration number

Publications

Association of methylenetetrahydrofolate reductase gene polymorphisms and maternal folic acid use with the risk of congenital heart disease.

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