Association of maternal dietary intakes and CBS gene polymorphisms with congenital heart disease in offspring

Li, Yihuan; Diao, Jingyi; Li, Jinqi; Luo, Liu; Zhao, Lijuan; Zhang, Senmao; Wang, Tingting; Chen, Letao; Yang, Tubao; Zhu, Ping; Qin, Jiabi

doi:10.1016/j.ijcard.2020.08.018

Cited by 13 publications

(13 citation statements)

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“…Folate deficiency plays an important role in the etiology of CHD [ 24 ]. Many studies have shown that the genetic variants of key enzyme genes in folate metabolism pathway, such as MTHFR, methionine synthase reductase (MTRR), methionine synthase (MTR) and cystathionine beta synthase (CBS) were significantly associated with the occurrence of CHD [ 22 , 25 , 26 ]. Here, we investigated the association of maternal MTHFR gene polymorphisms closely related to folate metabolism with the risk of CHD in offspring.…”

Section: Discussionmentioning

confidence: 99%

“…The face-to-face interview was adopted to complete the questionnaire by professionally trained investigators. The questionnaire used has been described in our previous published articles [ 22 ]. Here we collected maternal social demographic characteristics (e.g., age, education level, family income in the past 1 year, body mass index before this pregnancy, and residence location ), abnormal pregnancy history before this pregnancy (e.g., spontaneous abortion, induced abortion or labor, fetal death or stillbirth, premature delivery, low birth weight, neonatal death, ectopic pregnancy, hypertension of pregnancy, and gestational diabetes mellitus ), family history (e.g., consanguineous marriages and congenital malformations ), personal lifestyle and habit before this pregnancy in the 3 months before this pregnancy (e.g., active smoking, passive smoking, drinking, and drinking tea ), exposure history of environmental hazardous substance in the 3 months before this pregnancy (e.g., harmful chemicals, noise pollution exposure, newly renovated houses, dyeing or perming hair, and frequency of cosmetics use ) and medicine history in this pregnancy (e.g., folate use, macrolide antibiotics, and antidepressants ).…”

Section: Methodsmentioning

confidence: 99%

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Association analysis of maternal MTHFR gene polymorphisms and the occurrence of congenital heart disease in offspring

Sun

Wang

Huang

et al. 2021

BMC Cardiovasc Disord

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Background Although many studies showed that the risk of congenital heart disease (CHD) was closely related to genetic factors, the exact pathogenesis is still unknown. Our study aimed to comprehensively assess the association of single nucleotide polymorphisms (SNPs) of maternal MTHFR gene with risk of CHD and its three subtypes in offspring. Methods A case–control study involving 569 mothers of CHD cases and 652 health controls was conducted. Thirteen SNPs were detected and analyzed. Results Our study showed that genetic polymorphisms of maternal MTHFR gene at rs4846052 and rs1801131 were significantly associated with risk of CHD in the homozygote comparisons (TT vs. CC at rs4846052: OR = 7.62 [95%CI 2.95–19.65]; GG vs. TT at rs1801131: OR = 5.18 [95%CI 2.77–9.71]). And six haplotypes of G–C (involving rs4846048 and rs2274976), A–C (involving rs1801133 and rs4846052), G–T (involving rs1801133 and rs4846052), G–T–G (involving rs2066470, rs3737964 and rs535107), A–C–G (involving rs2066470, rs3737964 and rs535107) and G–C–G (involving rs2066470, rs3737964 and rs535107) were identified to be significantly associated with risk of CHD. Additionally, we observed that a two-locus model involving rs2066470 and rs1801131 as well as a three-locus model involving rs227497, rs1801133 and rs1801131 were significantly associated with risk of CHD in the gene–gene interaction analyses. For three subtypes including atrial septal defect, ventricular septal defect and patent ductus arteriosus, similar results were observed. Conclusions Our study indicated genetic polymorphisms of maternal MTHFR gene were significantly associated with risk of fetal CHD in the Chinese population. Additionally, there were significantly interactions among different SNPs on risk of CHD. However, how these SNPs affect the development of fetal heart remains unknown, and more studies in different ethnic populations and with a larger sample are required to confirm these findings.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Association analysis of maternal MTHFR gene polymorphisms and the occurrence of congenital heart disease in offspring

Sun

Wang

Huang

et al. 2021

BMC Cardiovasc Disord

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“…Study design and recruitment of study participants For requirements for a speci c article type please refer to the Article Types on any Frontiers journal page. The main characteristics of the participants and research procedure had been described by our previous study 34 . Recruitment was conducted by the Hunan Provincial Children's Hospital (Changsha, Hunan Province, China).…”

Section: Methodsmentioning

confidence: 99%

“…When mothers completed the questionnaires mentioned above, they were asked to provide 3 to 5 milliliters of peripheral venous blood for genotyping. Methods for DNA extraction and genotyping have been described previously 34 . The laboratory technician, who performed the genotyping, retyped and double-checked each sample, and recorded the genotype data, was blinded to whether the samples were from cases or controls.…”

Section: Sequencing Of Mthfd Gene and Genotypingmentioning

confidence: 99%

Association of MTHFD Gene Polymorphisms and Maternal Smoking With Risk of Congenital Heart Disease: A Hospital-Based Case-Control Study

Song¹,

Li²,

Diao³

et al. 2021

Preprint

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Background: MTHFD may affect the embryonic development by elevated homocysteine levels, DNA synthesis and DNA methylation, but limited number of genetic variants of MTHFD was focused on the association with congenital heart disease (CHD). This study examined the role of MTHFD and maternal smoking in 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 MTHFD gene. The logistic regression model was used for accessing the strength of association.Results: Mothers exposed to secondhand smoke during three 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 MTHFD 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. Furthermore, we found the different degrees of interaction effects between polymorphisms of the MTHFD gene including rs1950902, rs2236222, rs1256142, rs11849530 and rs2236225, and maternal tobacco exposure.Conclusions: Maternal polymorphisms of MTHFD gene at rs1950902, rs2236222, rs1256142 and rs11849530, maternal tobacco exposure and their interactions are significantly increased the risk of CHD in offspring. 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; http://www.chictr.org.cn/edit.aspx?pid=28300&htm=4

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“…Early work in our laboratory and other literature reveal that genetic polymorphisms of genes related to the maternal folate-homocysteine metabolism pathway, such as methylenetetrahydrofolate reductase (MTHFR) (7), cystathionine beta synthase (CBS) (8), and methionine synthase (MS) (9), are closely associated with the development of CHD. In this study, the gene of interest is methylenetetrahydrofolate dehydrogenase 1 (MTHFD1), which has gotten less attention than the abovementioned genes despite its importance in one-carbon folate metabolism.…”

Section: Introductionmentioning

confidence: 99%

Association of Maternal Dietary Habits and MTHFD1 Gene Polymorphisms With Ventricular Septal Defects in Offspring: A Case-Control Study

et al. 2022

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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.

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Association of maternal dietary intakes and CBS gene polymorphisms with congenital heart disease in offspring

Cited by 13 publications

References 32 publications

Association analysis of maternal MTHFR gene polymorphisms and the occurrence of congenital heart disease in offspring

Association analysis of maternal MTHFR gene polymorphisms and the occurrence of congenital heart disease in offspring

Association of MTHFD Gene Polymorphisms and Maternal Smoking With Risk of Congenital Heart Disease: A Hospital-Based Case-Control Study

Association of Maternal Dietary Habits and MTHFD1 Gene Polymorphisms With Ventricular Septal Defects in Offspring: A Case-Control Study

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