Maternal Obesity and Tobacco Use Modify the Impact of Genetic Variants on the Occurrence of Conotruncal Heart Defects

Details

• Alternative Title:
  PLoS One
• Personal Author:
  Tang, Xinyu ; Nick, Todd G. ; Cleves, Mario A. ; Erickson, Stephen W. ; Li, Ming ; Li, Jingyun ; MacLeod, Stewart L. ; Hobbs, Charlotte A.
• Description:
  Conotruncal heart defects (CTDs) are among the most severe birth defects worldwide. Studies of CTDs indicate both lifestyle behaviors and genetic variation contribute to the risk of CTDs. Based on a hybrid design using data from 616 case-parental and 1645 control-parental triads recruited for the National Birth Defects Prevention Study between 1997 and 2008, we investigated whether the occurrence of CTDs is associated with interactions between 921 maternal and/or fetal single nucleotide polymorphisms (SNPs) and maternal obesity and tobacco use. The maternal genotypes of the variants in the glutamate-cysteine ligase, catalytic subunit (GCLC) gene and the fetal genotypes of the variants in the glutathione S-transferase alpha 3 (GSTA3) gene were associated with an elevated risk of CTDs among obese mothers. The risk of delivering infants with CTDs among obese mothers carrying AC genotype for a variant in the GCLC gene (rs6458939) was 2.00 times the risk among those carrying CC genotype (95% confidence interval: 1.41, 2.38). The maternal genotypes of several variants in the glutathione-S-transferase (GST) family of genes and the fetal genotypes of the variants in the GCLC gene interacted with tobacco exposures to increase the risk of CTDs. Our study suggests that the genetic basis underlying susceptibility of the developing heart to the adverse effects of maternal obesity and tobacco use involve both maternal and embryonic genetic variants. These results may provide insights into the underlying pathophysiology of CTDs, and ultimately lead to novel prevention strategies.
• Subjects:
  Case-Control Studies Chromosomes, Human Female Gene-Environment Interaction Genetic Predisposition To Disease Genetic Variation Heart Defects, Congenital Humans Mothers Obesity Polymorphism, Single Nucleotide Signal Transduction Tobacco Use

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• Source:
  PLoS One. 2014; 9(10).
• Pubmed ID:
  25275547
• Pubmed Central ID:
  PMC4183535
• Document Type:
  Journal Article
• Funding:
  5R01HD039054-12/HD/NICHD NIH HHS/United States ; 5U01DD000491-05/DD/NCBDD CDC HHS/United States ; R01 HD039054/HD/NICHD NIH HHS/United States
• Place as Subject:
  United States
• Volume:
  9
• Issue:
  10
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:a8efe146ab954564521bd5ee31ab044c2d2e56661bdf93d2b0f524e199b8953d
• Download URL:
  https://stacks.cdc.gov/view/cdc/32193/cdc_32193_DS1.pdf
• File Type:
  [PDF - 1.55 MB ]