title: Indoor air pollution and neural tube defects: effect modification by maternal genes.
abstract: BACKGROUND
  Gene-environment interactions have been implicated in the development of neural tube defects (NTDs).
  
  
  METHODS
  We conducted a case-control study to investigate (1) the association of aryl hydrocarbon receptor (AHR) genetic variants and phase I metabolic enzymes with the risk of NTDs and (2) the interaction of these variants with maternal exposure to indoor air pollution from smoking and coal combustion or with placental polycyclic aromatic hydrocarbons (PAHs). Blood samples were collected from 534 mothers of fetuses or newborns with NTDs and 534 control mothers who had healthy term newborns and were assayed for 12 polymorphisms in the AHR and cytochrome P450 (CYP) genes. Information on maternal exposure was collected, and placental levels of PAHs were analyzed.
  
  
  RESULTS
  Maternal exposure to indoor air pollution was associated with an increased NTD risk. However, no increased NTD risk was observed for individual genetic variants. For mothers with the CYP1B1 rs2855658 GG variant, exposure to indoor air pollution led to a dose-response relationship for NTD risk, with odds ratios (ORs) of 3.0 (95% confidence interval = 1.6-5.7) and 8.1 (3.8-17) for medium and high levels of exposure, respectively. For mothers with GA or AA genotypes, this trend was less apparent. Placental PAHs were associated with an increased risk of NTDs, with an OR of 16 (3.3-75) for high levels compared with low levels of exposure among mothers with the GG genotype; there was no association for mothers with GA or AA genotypes.
  
  
  CONCLUSIONS
  The CYP1B1 variant modifies the effect of indoor air pollution on NTD risk.
authors: From the aInstitute of Reproductive and Child Health/Ministry of Health Key Laboratory of Reproductive Health, School of Public Health, Peking University, Beijing, China; and bDepartment of Epidemiology and Health Statistics, School of Public Health, Peking University, Beijing, China.
authors: Linlin
authors: L
authors: Wang
authors: Zhiwen
authors: Z
authors: Li
authors: Lei
authors: L
authors: Jin
authors: Kai
authors: K
authors: Li
authors: Yue
authors: Y
authors: Yuan
authors: Yunting
authors: Y
authors: Fu
authors: Yali
authors: Y
authors: Zhang
authors: Rongwei
authors: R
authors: Ye
authors: Aiguo
authors: A
authors: Ren
mesh_terms: D000328:Adult; D000393:Air Pollutants / Q000032:analysis / Q000633:toxicity; D016902:Air Pollution, Indoor / Q000009:adverse effects* / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D065633:Cytochrome P-450 CYP1B1 / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D016015:Logistic Models; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D009436:Neural Tube Defects / Q000209:etiology*; D016017:Odds Ratio; D010920:Placenta / Q000737:chemistry; D011084:Polycyclic Aromatic Hydrocarbons / Q000032:analysis / Q000633:toxicity; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics*; D012307:Risk Factors; D057566:Self Report
chemical_list: D000393:Air Pollutants; D015415:Biomarkers; D005819:Genetic Markers; D011084:Polycyclic Aromatic Hydrocarbons; D018336:Receptors, Aryl Hydrocarbon; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1