Genetic variation in biotransformation enzymes, air pollution exposures, and risk of spina bifida

Am J Med Genet A. 2018 May;176(5):1055-1090. doi: 10.1002/ajmg.a.38661.


Spina bifida is a birth defect characterized by incomplete closure of the embryonic neural tube. Genetic factors as well as environmental factors have been observed to influence risks for spina bifida. Few studies have investigated possible gene-environment interactions that could contribute to spina bifida risk. The aim of this study is to examine the interaction between gene variants in biotransformation enzyme pathways and ambient air pollution exposures and risk of spina bifida. We evaluated the role of air pollution exposure during pregnancy and gene variants of biotransformation enzymes from bloodspots and buccal cells in a California population-based case-control (86 cases of spina bifida and 208 non-malformed controls) study. We considered race/ethnicity and folic acid vitamin use as potential effect modifiers and adjusted for those factors and smoking. We observed gene-environment interactions between each of the five pollutants and several gene variants: NO (ABCC2), NO2 (ABCC2, SLC01B1), PM10 (ABCC2, CYP1A1, CYP2B6, CYP2C19, CYP2D6, NAT2, SLC01B1, SLC01B3), PM2.5 (CYP1A1 and CYP1A2). These analyses show positive interactions between air pollution exposure during early pregnancy and gene variants associated with metabolizing enzymes. These exploratory results suggest that some individuals based on their genetic background may be more susceptible to the adverse effects of pollution.

Keywords: air pollution; congenital anomalies; gene; gene-environment; spina bifida.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Air Pollution / adverse effects*
  • Alleles
  • Biotransformation / genetics*
  • Carbon Monoxide / adverse effects
  • Case-Control Studies
  • Databases, Genetic
  • Environmental Exposure
  • Female
  • Gene Expression Regulation, Enzymologic*
  • Gene-Environment Interaction
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Genetic Testing
  • Genetic Variation*
  • Humans
  • Male
  • Middle Aged
  • Nitrogen Oxides / adverse effects
  • Odds Ratio
  • Particulate Matter / adverse effects
  • Risk Assessment
  • Risk Factors
  • Spinal Dysraphism / etiology*
  • Young Adult


  • Nitrogen Oxides
  • Particulate Matter
  • Carbon Monoxide