title: Genetic variation affects congenital heart defect susceptibility in offspring exposed to maternal tobacco use.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Biostatistics Program, Department of Pediatrics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Tang
authors.affiliation: Division of Birth Defects Research, Department of Pediatrics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Hobbs
authors.affiliation: Division of Birth Defects Research, Department of Pediatrics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Mario A
authors.initials: MA
authors.lastname: Cleves
authors.affiliation: Department of Biostatistics, College of Public Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Erickson
authors.affiliation: Division of Birth Defects Research, Department of Pediatrics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Stewart L
authors.initials: SL
authors.lastname: MacLeod
authors.affiliation: Division of Birth Defects Research, Department of Pediatrics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Sadia
authors.initials: S
authors.lastname: Malik
mesh_terms: D000328:Adult; D005260:Female; D020022:Genetic Predisposition to Disease; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D018811:Maternal Exposure / Q000009:adverse effects*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D012907:Smoking / Q000009:adverse effects / Q000235:genetics
keywords: congenital heart defects; genetic variants; national birth defects prevention study; single nucleotide polymorphisms; tobacco use