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Genetic variation affects congenital heart defect susceptibility in offspring exposed to maternal tobacco use.

ABSTRACT: Congenital heart defects (CHDs) are among the most prevalent and serious birth defects, occurring in 8 to 10 of every 1000 live births in the United States. Epidemiologic studies have reported an association between CHDs and maternal smoking, but it remains unknown how genes impact the susceptibility of offspring to CHDs in the presence of maternal tobacco use.Using data from 403 case- and 219 control-parental triads enrolled in the National Birth Defects Prevention Study between 1998 and 2008, we investigated the association between CHDs and maternal and infant genetic variants involved in the tobacco metabolism and DNA repair pathways among mothers who smoked prenatally.The maternal genotypes of single nucleotide polymorphisms in the excision repair cross-complementation group 1 (ERCC1), poly (ADP-ribose) polymerase 2 (PARP2), and ERCC5 genes were identified to be significantly associated with the occurrence of CHDs in the presence of maternal tobacco use. Our analysis also revealed a moderate association between the infant genotypes of polymorphisms in the O-sialoglycoprotein endopeptidase (OSGEP) gene and increased risk of CHDs among mothers who smoked.Our study provides evidence that maternal and infant polymorphisms within the ERCC1, PARP2, ERCC5, and OSGEP genes are associated with CHD risk in the presence of maternal tobacco use. These results may provide insight into the susceptibility of having a pregnancy affected by CHDs among women who smoke.

SUBMITTER: Tang X

PROVIDER: S-EPMC4774247 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Genetic variation affects congenital heart defect susceptibility in offspring exposed to maternal tobacco use.

Tang Xinyu X Hobbs Charlotte A CA Cleves Mario A MA Erickson Stephen W SW MacLeod Stewart L SL Malik Sadia S

Birth defects research. Part A, Clinical and molecular teratology 20150602 10

<h4>Background</h4>Congenital heart defects (CHDs) are among the most prevalent and serious birth defects, occurring in 8 to 10 of every 1000 live births in the United States. Epidemiologic studies have reported an association between CHDs and maternal smoking, but it remains unknown how genes impact the susceptibility of offspring to CHDs in the presence of maternal tobacco use.<h4>Methods</h4>Using data from 403 case- and 219 control-parental triads enrolled in the National Birth Defects Preve ...[more]

PMID: 26033827

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Project description:BackgroundCongenital heart defects (CHDs) are the most common congenital malformations. The aetiology of CHDs is complex. Large cohort studies and systematic reviews and meta-analyses based on these have reported an association between higher risk of CHDs in the offspring and individual maternal metabolic disorders such as obesity, diabetes, hypertension, and preeclampsia, all conditions that can be related to insulin resistance or hyperglycaemia. However, the clinical reality is that these conditions often occur simultaneously. The aim of this review is, in consequence, both to evaluate the existing evidence on the association between maternal metabolic disorders, defined as obesity, diabetes, hypertension, preeclampsia, dyslipidaemia and CHDs in the offspring, as well as the significance of combinations, such as metabolic syndrome, as risk factors.MethodsA systematic literature search of papers published between January 1, 1990 and January 14, 2021 was conducted using PubMed and Embase. Studies were eligible if they were published in English and were case-control or cohort studies. The exposures of interest were maternal overweight or obesity, hypertension, preeclampsia, diabetes, dyslipidaemia, and/or metabolic syndrome, and the outcome of interest was CHDs in the offspring. Furthermore, the studies were included according to a quality assessment score.ResultsOf the 2,250 identified studies, 32 qualified for inclusion. All but one study investigated only the individual metabolic disorders. Some disorders (obesity, gestational diabetes, and hypertension) increased risk of CHDs marginally whereas pre-gestational diabetes and early-onset preeclampsia were strongly associated with CHDs, without consistent differences between CHD subtypes. A single study suggested a possible additive effect of maternal obesity and gestational diabetes.ConclusionsFuture studies of the role of aberrations of the glucose-insulin homeostasis in the common aetiology and mechanisms of metabolic disorders, present during pregnancy, and their association, both as single conditions and-particularly-in combination, with CHDs are needed.

Project description:BackgroundAlthough there is evidence in experimental model systems that exposure to polycyclic aromatic hydrocarbons (PAHs) is linked with congenital heart defects (CHDs), few studies have examined the association in humans. We conducted a case-control study to examine the association between maternal exposure to PAHs and CHDs in offspring using data from the National Birth Defects Prevention Study (NBDPS) (1997-2011).MethodsWe obtained detailed information on maternal occupation during the month before to three months after conception. Expert raters, masked to case-control status, assessed job descriptions to assign categorical levels of exposure. Categories were quantitatively mapped to estimate cumulative exposure to PAHs, incorporating exposure intensity, frequency, work duration, and work hours. Quartiles were generated for cumulative maternal exposure to PAHs. Crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using unconditional logistic regression for quartiles of PAH exposure and six CHD groupings (e.g. conotruncal) and specific subtypes (e.g. tetralogy of Fallot [ToF]). Final models were adjusted for maternal age, race/ethnicity, education, smoking, anticonvulsant use, folic acid supplementation, and study center.ResultsThere were 4,775 case and 7,734 control infants eligible for the study. The prevalence of occupational exposure to PAHs was 10.2% among both case and control mothers. In adjusted analysis, compared to mothers with no occupational PAH exposure, those in the highest quartile of exposure were more likely to have offspring in the conotruncal heart defects group (OR 1.41; 95% CI 1.00-2.00), and with ToF (OR 1.83; 95% CI 1.21-2.78).ConclusionsWomen in the highest quartile of estimated cumulative occupational PAH exposure during early pregnancy were more likely to have offspring with conotruncal heart defects, specifically ToF, compared to women with no occupational PAH exposure. Other comparisons between PAHs and other CHDs subgroups did not show any statistically precise associations.

Dataset Information

Genetic variation affects congenital heart defect susceptibility in offspring exposed to maternal tobacco use.

Publications

Genetic variation affects congenital heart defect susceptibility in offspring exposed to maternal tobacco use.

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