title: Increased risk for congenital heart defects in children carrying the ABCB1 Gene C3435T polymorphism and maternal periconceptional toxicants exposure.
abstract: BACKGROUND
  The 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.
  
  
  METHODS
  An 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.
  
  
  RESULTS
  MATERNAL 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Department of Pediatric Cardiovascular Disease, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Wang
authors.forename: Liang
authors.initials: L
authors.lastname: Xie
authors.forename: Kaiyu
authors.initials: K
authors.lastname: Zhou
authors.forename: Yalan
authors.initials: Y
authors.lastname: Zhan
authors.forename: Yifei
authors.initials: Y
authors.lastname: Li
authors.forename: Huaying
authors.initials: H
authors.lastname: Li
authors.forename: Lina
authors.initials: L
authors.lastname: Qiao
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Yimin
authors.initials: Y
authors.lastname: Hua
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D002675:Child, Preschool; D002681:China; D017931:DNA Primers; D005006:Ethnicity; D005260:Female; D020022:Genetic Predisposition to Disease; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D018811:Maternal Exposure; D010636:Phenols / Q000633:toxicity; D010795:Phthalic Acids / Q000633:toxicity; D011110:Polymorphism, Genetic; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D013723:Teratogens
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D017931:DNA Primers; D010636:Phenols; D010795:Phthalic Acids; D012333:RNA, Messenger; D013723:Teratogens