Dataset Information

Association of Maternal Diabetes Mellitus and Polymorphisms of the NKX2.5 Gene in Children with Congenital Heart Disease: A Single Centre-Based Case-Control Study.

ABSTRACT: Background:Congenital heart disease (CHD) is one of the most common birth defects among newborns, accounting for a large proportion of infant mortality worldwide. However, the mechanisms remain largely undefinable. This study aimed to investigate the association of CHD in offspring of mothers with diabetes mellitus (DM) and single nucleotide polymorphisms (SNPs) of NKX2.5. Methods and Results:A case-control study of 620 mothers of CHD patients and 620 mothers of healthy children admitted to Hunan Children's Hospital from November 2017 to December 2019 was conducted. We collected the mothers' information by questionnaire and detected children's NKX2.5 variants with a MassARRAY system. The interaction coefficient (?) was used to quantify the estimated gene-environment interactions. Univariate and multivariate analyses both showed that the infants had a higher risk of CHD if their mothers had a history of DM, including gestational DM (GDM) during this pregnancy (adjusted odds ratio [aOR = 4.98]), GDM in previous pregnancies (aOR = 4.30), and pregestational DM (PGDM) in the 3 months before this pregnancy (aOR = 6.78). Polymorphisms of the NKX2.5 gene at rs11802669 (C/C vs. T/T: aOR = 4.97; C/T vs. T/T: aOR = 2.15) and rs2277923 (T/T vs. C/C, aOR = 1.74; T/C vs. C/C, aOR = 1.61) were significantly associated with the risk of CHD in offspring. In addition, significant interactions between maternal DM and NKX2.5 genetic variants at rs11802669 (aOR = 8.12) and rs2277923 (aOR = 17.72) affecting the development of CHD were found. Conclusions:These results suggest that maternal DM, NKX2.5 genetic variants, and their interactions are significantly associated with the risk of CHD in offspring.

SUBMITTER: Zhao M

PROVIDER: S-EPMC7533784 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Association of Maternal Diabetes Mellitus and Polymorphisms of the <i>NKX2.5</i> Gene in Children with Congenital Heart Disease: A Single Centre-Based Case-Control Study.

Zhao Mingyi M Diao Jingyi J Huang Peng P Li Jinqi J Li Yihuan Y Yang Yang Y Luo Liu L Zhang Senmao S Chen Letao L Wang Tingting T Wang Tingting T Zhu Ping P Qin Jiabi J

Journal of diabetes research 20200925

<h4>Background</h4>Congenital heart disease (CHD) is one of the most common birth defects among newborns, accounting for a large proportion of infant mortality worldwide. However, the mechanisms remain largely undefinable. This study aimed to investigate the association of CHD in offspring of mothers with diabetes mellitus (DM) and single nucleotide polymorphisms (SNPs) of <i>NKX2.5</i>.<h4>Methods and results</h4>A case-control study of 620 mothers of CHD patients and 620 mothers of healthy chi ...[more]

PMID: 33062711

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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:BackgroundMTHFD1 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.MethodsA 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.ResultsMothers 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.ConclusionsMaternal 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 registrationRegistration number: ChiCTR1800016635 .

Dataset Information

Association of Maternal Diabetes Mellitus and Polymorphisms of the NKX2.5 Gene in Children with Congenital Heart Disease: A Single Centre-Based Case-Control Study.

Publications

Association of Maternal Diabetes Mellitus and Polymorphisms of the <i>NKX2.5</i> Gene in Children with Congenital Heart Disease: A Single Centre-Based Case-Control Study.

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