Abstract
BackgroundsThe etiology of congenital heart defect (CHD) is commonly believed to involve the interaction of multiple environmental and genetic factors. This study aimed to explore the joint effects of the ABCB1 gene C3435T polymorphism and maternal periconceptional toxicants exposure on the CHD risk in a Han Chinese population.MethodsAn age and gender matched case-control study with standardized data collection involving 201 pairs was conducted. Periconceptional toxicants exposure was obtained through a structured questionnaire. A job exposure matrix (JEM) was used for toxicants exposure assessment. Genotyping of the ABCB1 C3435T polymorphism was performed by sequencing. Logistic regression analysis was performed to assess the joint effects of the ABCB1 gene C3435T polymorphism and toxicants exposure on the risk of CHD. Placenta tissues and umbilical cords were collected to investigate the impact of C3435T polymorphism on the transcription and translation activities of ABCB1 gene.ResultsMaternal periconceptional exposures to phthalates (adjusted OR: 1.6; 95%CI: 1.0–2.6) and alkylphenolic compounds (adjusted OR:1.8; 95%CI:1.1–3.0) were associated with a higher incidence of CHDs in general. More cases were carriers of the ABCB1 CC/CT genotypes (OR: 2.0, 95%CI: 1.1–3.5, P-value: 0.021). Children carrying the CC/CT genotype and periconceptionally exposed to phthalates and alkylphenolic compounds suffered almost 3.5-fold increased risk of having CHD than non-exposed children with TT genotype (adjusted OR: 3.5, 95%CI: 1.5–7.9, P-value: 0.003), and the OR changed to 4.4 for septal defects (adjusted OR: 4.4,95%CI:1.8–10.9,P-value:0.001). The ABCB1 mRNA expression of the TT genotype was significantly higher than that of the CC genotype (P = 0.03). Compared with TT genotype, lower P-glycoprotein expression was observed for the CC/CT genotypes.ConclusionThe C3435T polymorphism in the ABCB1 gene of fetus increases the risks of CHD in a Han Chinese population when the mothers are exposed to phthalates and alkylphenolic compounds during the periconceptional period, particularly for septal defects.
Highlights
Worldwide congenital heart defect (CHD) is one of the most common birth defects, occurring in 7 to 8 per 1000 live births in China
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
After adjusting for confounding factors mentioned in the statistical analysis, the results showed that both maternal periconceptionally exposures to phthalates and alkylphenolic compounds were associated with a higher incidence of CHDs in general
Summary
Worldwide congenital heart defect (CHD) is one of the most common birth defects, occurring in 7 to 8 per 1000 live births in China. Substantial epidemiological data have demonstrated that the exposure to several toxicants during the periconceptional period was associated with an increased risk of CHD [3,4,5,6]. Not all women exposed to toxicants during the periconceptional period give birth to a child with CHD. The reasons for such phenomenon still remain elusive. There is increasing evidence that the placenta expresses a range of transporters capable of controlling the transplacental disposition of many toxicant agents and thereby playing a crucial role in fetal protection against maternal toxins [7,8,9,10,11,12,13]. Of main interest are the ATP-binding cassette (ABC) transporters, the first discovered and so far the best characterized of drug
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