Associations and interaction effects of maternal smoking and genetic polymorphisms of cytochrome P450 genes with risk of congenital heart disease in offspring: A case-control study.
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ABSTRACT: Abstract
To assess associations and interactions of maternal smoking and cytochrome P450 (CYP450) genetic variants with the developments of congenital heart disease (CHD) and specific subtypes.A case-control study of 654 cases and 666 controls was conducted from November 2017 to March 2020. The exposures of interest were maternal active and passive smoking before/in the early pregnancy and CYP450 genetic polymorphisms. Data were analyzed using the Chi-square test and logistic regression analysis.After adjusting for the potential confounding factors, our study showed maternal active (ORadj = 2.34, 95%CI: 1.19-4.60) or passive (ORadj = 1.76, 95%CI: 1.34-2.31) smoking before pregnancy, passive smoking in the early pregnancy (ORadj = 3.05, 95%CI: 2.26-4.12), as well as polymorphisms of CYP450 at rs1065852 (G/A vs G/G: ORadj = 1.46, 95%CI: 1.07-1.99; A/A vs G/G: ORadj = 1.63, 95%CI: 1.15-2.33) and rs16947 (A/A vs G/G: ORadj = 3.61, 95%CI: 2.09-6.23), were significantly associated with risk of total CHD in offspring. Similar results were also found for some subtypes of CHD. Additionally, significant interactions between maternal smoking and CYP450 genes on the risk of CHD were observed.Maternal smoking and CYP450 genetic variants were associated with increased risk of CHD and specific subtypes in offspring. And the effects of CYP450 genes on CHD may be modified by maternal smoking.
SUBMITTER: Diao J
PROVIDER: S-EPMC8202638 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC7939180 | biostudies-literature
Project description:BackgroundIn general, the existing evidence points to a role for maternal sleep in pregnancy complications and fetal growth, however, little has been focused on birth defects. We aimed to explore the association between periconceptional poor sleep and the risk of congenital heart disease (CHD), and to examine if daytime napping could to some extent change the association.MethodsA case-control study was conducted in Shanghai Children's Medical Center, in which, a total of 524 cases (262 simple CHD vs. 262 severe CHD), along with 262 controls.ResultsIn the multivariable logistic analysis, poor sleep could increase the risk of both simple CHD (OR = 2.486, 95% CI = 1.619-3.818) and severe CHD (OR = 1.950, 95% CI = 1.269-2.997), while routine daytime nap could decrease risk of simple CHD (OR = 0.634, 95% CI = 0.435-0.923). In the stratified analysis, the concurrence with routine daytime nap could weaken the risk of simple CHD caused by poor sleep (OR = 3.183, 95% CI: 1.830-5.537 decreased to OR = 2.236, 95% CI: 1.200-4.165). The examinations were repeated in ventricular septal defect and tetralogy of Fallot, and the established associations can be verified. Moreover, all these findings were also similarly observed in both propensity-score-adjusted and propensity-score-matched analyses.ConclusionsPoor maternal sleep around periconceptional period seems to be an independent risk factor for CHD. The concurrence with daytime nap could to some extent reduce the risk in simple CHD. The results individually and collectively put forward the importance of maternal sleep in embryonic heart development.
| S-EPMC7432175 | biostudies-literature
Project description:BackgroundAlthough 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.MethodsA case-control study involving 569 mothers of CHD cases and 652 health controls was conducted. Thirteen SNPs were detected and analyzed.ResultsOur 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.ConclusionsOur 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.
| S-EPMC8204503 | biostudies-literature
Project description:BackgroundThe relationship between prenatal tobacco exposure and hyperactivity remains controversial. To mitigate limitations of prior studies, we used a strategy involving comparison of maternal and paternal smoking reports in a historical sample where smoking during pregnancy was common.MethodData were drawn from a longitudinally followed subsample of the Child Health and Development Study (n = 1752), a population-based pregnancy cohort ascertained in 1961-1963 in California. Maternal prenatal smoking was common (33.4%). Maternal and paternal smoking patterns were assessed at three time points by mother report. Hyperactivity was assessed at the mean of age of 10 years based on mother report to a personality inventory.ResultsUnadjusted, maternal smoking during pregnancy was associated with offspring hyperactivity [β = 0.22, 95% confidence interval (CI) 0.11-0.33] and, to a similar degree, when the father smoked (β = 0.18, 95% CI 0.07-0.30). After adjustment, maternal smoking remained robustly predictive of offspring hyperactivity (β = 0.25, 95% CI 0.09-0.40) but father smoking was not (β = 0.02, 95% CI -0.20 to 0.24). When examined among the pairs matched on propensity score, mother smoking was robustly related to offspring hyperactivity whether the father smoked (β = 0.26, 95% CI 0.03-0.49) or did not smoke (β = 0.30, 95% CI 0.04-0.57). By number of cigarettes, associations with hyperactivity were present for 10-19 and 20+ cigarettes per day among mothers.ConclusionsIn a pregnancy cohort recruited in a time period in which smoking during pregnancy was common, we document associations between prenatal smoking exposure and offspring hyperactivity. Novel approaches to inferring causality continue to be necessary in describing the potential adverse consequences of prenatal smoking exposure later in life.
| S-EPMC4615686 | biostudies-literature
Project description:ObjectiveTo study the association between maternal reduced folate carrier (RFC) gene polymorphisms and congenital heart disease (CHD) in offspring.MethodsA hospital-based case-control study was conducted. The mothers of 683 infants with CHD who attended the Department of Cardiothoracic Surgery, Hunan Children's Hospital, from November 2017 to March 2020 were enrolled as the case group. The mothers of 740 healthy infants without any deformity who attended the hospital during the same period of time were enrolled as the control group. A questionnaire survey was performed to collect the exposure data of subjects. Venous blood samples of 5 mL were collected from the mothers for genetic polymorphism detection. A multivariate logistic regression analysis was used to evaluate the association of RFC gene polymorphisms and their haplotypes with CHD. A generalized multifactor dimensionality reduction method was used to analyze gene-gene interactions.ResultsAfter control for confounding factors, the multivariate logistic regression analysis showed that maternal RFC gene polymorphisms at rs2236484 (AG vs AA:OR=1.91, 95%CI:1.45-2.51; GG vs AA: OR=1.96, 95%CI:1.40-2.75) and rs2330183 (CT vs CC:OR=1.39, 95%CI:1.06-1.83) were significantly associated with the risk of CHD in offspring. The haplotypes of G-G (OR=1.21, 95%CI:1.03-1.41) and T-G (OR=1.25, 95%CI:1.07-1.46) in mothers significantly increased the risk of CHD in offspring. The interaction analysis showed significant gene-gene interactions between different SNPs of the RFC gene in CHD (P < 0.05).ConclusionsMaternal RFC gene polymorphisms and interactions between different SNPs are significantly associated with the risk of CHD in offspring.
| S-EPMC8214001 | biostudies-literature
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.
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Project description:Physiological plasticity in a polluted system: A case of an uncultured bacterium and its cypome
| PRJEB38781 | ENA
Project description:OBJECTIVE:Obesity is a risk factor for congenital heart defects (CHDs), but whether risk is independent of abnormal glucose metabolism remains unknown. Data on whether overweight status increases the risk are also conflicting. RESEARCH DESIGN AND METHODS:We included 121?815 deliveries from a cohort study, the Consortium on Safe Labor (CSL), after excluding women with pregestational diabetes as recorded in the electronic medical record. CHD was identified via medical record discharge summaries. Adjusted odds ratios (ORs) for any CHD were calculated for prepregnancy body mass index (BMI) categories of overweight (25-<30?kg?m(-2)), obese (30-<40?kg?m(-2)) and morbidly obese (?40?kg?m(-2)) compared with normal weight (18.5-<25?kg?m(-2)) women, and for specific CHD with obese groups combined (?30?kg?m(-2)). A subanalysis adjusting for oral glucose tolerance test (OGTT) results where available was performed as a proxy for potential abnormal glucose metabolism present at the time of organogenesis. RESULTS:There were 1388 (1%) infants with CHD. Overweight (OR=1.15, 95% confidence interval (95% CI): 1.01-1.32), obese (OR=1.26, 95% CI: 1.09-1.44) and morbidly obese (OR=1.34, 95% CI: 1.02-1.76) women had greater OR of having a neonate with CHD than normal weight women (P<0.001 for trend). Obese women (BMI?30?kg?m(-2)) had higher OR of having an infant with conotruncal defects (OR = 1.33, 95% CI: (1.03–1.72) [corrected], atrial septal defects (OR=1.22, 95% CI: 1.04-1.43) and ventricular septal defects (OR=1.38, 95% CI: 1.06-1.79). Being obese remained a significant predictor of CHD risk after adjusting for OGTT. CONCLUSION:Increasing maternal weight class was associated with an increased risk for CHD. In obese women, abnormal glucose metabolism did not completely explain the increased risk for CHD; the possibility that other obesity-related factors are teratogenic requires further investigation.
| S-EPMC4053485 | biostudies-literature
Project description:Maternal cigarette smoking is a risk factor for congenital heart defects (CHDs). Nicotine replacement therapies are often offered to pregnant women following failed attempts of smoking cessation. However, the impact of nicotine on embryonic heart development is not well understood. In the present study, the effects of maternal nicotine exposure (MNE) during pregnancy on foetal heart morphogenesis were studied. Adult female mice were treated with nicotine using subcutaneous osmotic pumps at 0.75 or 1.5 mg/kg/day and subsequently bred with male mice. Our results show that MNE dose-dependently increased CHDs in foetal mice. CHDs included atrial and ventricular septal defects, double outlet right ventricle, unguarded tricuspid orifice, hypoplastic left ventricle, thickened aortic and pulmonary valves, and ventricular hypertrophy. MNE also significantly reduced coronary artery size and vessel abundance in foetal hearts. Moreover, MNE resulted in higher levels of oxidative stress and altered the expression of key cardiogenic regulators in the developing heart. Nicotine exposure reduced epicardial-to-mesenchymal transition in foetal hearts. In conclusion, MNE induces CHDs and coronary artery malformation in mice. These findings provide insight into the adverse outcomes of foetuses by MNE during pregnancy.
| S-EPMC9170818 | biostudies-literature
Project description:BackgroundPrior studies suggested that maternal smoking before and during pregnancy could be associated with increased risks of congenital heart diseases (CHDs) in offspring. However, the results were inconsistent, and the existence of a causal relationship was not confirmed. Our study aimed to estimate the associations of maternal active and passive smoking during the pre-pregnancy/early-pregnancy period with CHDs as well as its common phenotypes in offspring.MethodsThis study was based on data from a prospective cohort study conducted in Central China. A total of 49 158 eligible pregnant women between the 8th and 14th weeks of gestation were invited to join the cohort and were planned to be followed up until 3 months postpartum. The exposure of interest was maternal smoking status, including active and passive smoking status in 3 months before pregnancy as well as in early pregnancy. Self-reported maternal smoking status was ascertained via an in-person interview after recruitment. CHDs were diagnosed by pediatric cardiologists and classified according to ICD-10. Multivariable Poisson regression models were used to estimate the relative risks (RRs) with 95% confidence intervals (CIs) of all CHDs and their common phenotypes associated with maternal smoking status, adjusting for potential confounding factors identified by directed acyclic graphs.ResultsCHDs were diagnosed in 564 children. After adjusting for potential confounding factors and comparing with the unexposed groups, CHDs incidence was 165% higher (adjusted RR = 2.65; 95% CI = 1.76-3.98) in offspring exposed to maternal active smoking in 3 months before pregnancy, 69% higher (adjusted-RR = 1.69; 95% CI = 1.39-2.05) in offspring exposed to maternal passive smoking in 3 months before pregnancy, 133% higher (adjusted RR = 2.33; 95% CI = 1.46-3.70) for offspring exposed to maternal active smoking in early pregnancy, and 98% higher (adjusted-RR = 1.98; 95% CI = 1.56-2.51) for offspring exposed to maternal passive smoking in early pregnancy. More specifically, the offspring exposed to maternal active smoking in early pregnancy had the highest risk of Tetralogy of Fallot (adjusted RR = 9.84; 95% CI = 2.49-38.84). These findings were recapitulated in analyses that further adjusted for other behaviour variables apart from the characteristic being assessed and were also confirmed by sensitivity analyses.ConclusionsOur findings add to the existing body of evidence that implicates maternal pre-pregnancy/early-pregnancy smoking as a significant risk factor for CHDs and their select phenotypes.
| S-EPMC9344981 | biostudies-literature