Effect modification of CPY2E1 and GSTZ1 genetic polymorphisms on associations between prenatal disinfection by-products exposure and birth outcomes.

ABSTRACT

BACKGROUND: Prenatal disinfection by-products (DBPs) exposure is linked with adverse birth outcomes. Genetic susceptibility to DBP metabolism may modify the exposure-outcome associations. OBJECT To investigate whether CYP2E1 and GSTZ1 genetic polymorphisms modified the associations of prenatal DBP exposures with adverse birth outcomes. METHODS: Two biomarkers of DBP exposures including trihalomethanes (THMs) in blood and trichloroacetic acid (TCAA) in urine were determined among 426 pregnant women from a Chinese cohort study. CYP2E1 (rs2031920, rs3813867, and rs915906) and GSTZ1 (rs7975) polymorphisms in cord blood were genotyped. Statistical interactions between prenatal DBP exposures and newborns CYP2E1 and GSTZ1 polymorphisms on birth outcomes (birth weight, birth length, and gestational age) were examined by multivariable linear regression with adjustment for potential confounders. RESULTS: We found that newborns CYP2E1 genetic polymorphisms (rs2031920 and rs3813867) modified the associations of maternal blood THMs or urinary TCAA levels with birth outcomes. However, these interactions were nonsignificant after Bonferroni correction for multiple comparisons, except for the interaction between maternal blood BrTHMs [sum of dibromochloromethane (DBCM), bromodichloromethane (BDCM), and bromoform (TBM)] and newborns CYP2E1 gene rs2031920 polymorphisms on birth weight (P for interaction = 0.003). CONCLUSION: Newborns genetic variations of CYP2E1 rs2031920 may modify the impacts of prenatal BrTHM exposure on birth weight. This finding needs to be further confirmed.