Genetic modification of maternal ETS exposure on child behavior: CYP1A1 impact

1. CYP1A1 modifies the effect of maternal exposure to environmental tobacco smoke on child behaviorCJ Hsieh1, SF Jeng2, YN Su4, HF Liao2, KY Wu3, WS Hsieh4, PC Chen11National Taiwan University College of Public Health; 2National Taiwan University College of Medicine;3National Health Research Institutes, Taiwan; 4National Taiwan University Hospital Background and Objective Results and Discussion Maternal ETS exposure was associated with the anxious score. The ETS exposed group with variant types of both the CYP1A1 MspI and CYP1A1 Ile462Val genes had a significantly poorer total CBCL score ( =15.30; p =0.014), as well as more internalizing ( =4.58; p =0.039), emotional ( =1.83; p =0.013), anxious ( =1.77; p =0.013), externalizing ( =5.30; p =0.019) and aggressive ( =4.29; p =0.023) behaviors and sleep problems ( =1.68; p =0.021), in multiple linear regression models. Material and Methods • Maternal environmental tobacco smoke (ETS) has been identified as a key risk factor for problem behavior in children, but the role of genetic susceptibility is not clear. The purpose of this study was to examine the metabolic genetic modification effect of exposure to ETS in non smokingmothers on child behavior at two years of age. A prospective cohort study was conducted among 191 mothers who gave births between 2004 and 2005 and their infants in Taiwan. The mothers completed a questionnaire before delivery in which they provided information on exposure to ETS during pregnancy. Four metabolic genes, CYP1A1 MspI, CYP1A1 Ile462Val, GSTT1 and GSTM1 were isolated from both maternal and infant DNA samples. Children’s behavior problems at two years of age were reported by their mothers using the Child Behavior Checklist/1½-5 (CBCL/1½-5). The CBCL yields internalizing, externalizing and sleep scores to evaluate the behavior problems. We used multiple linear models to estimate the effects of ETS and genotype on child behavior. Table 1. Characteristics of the study subjects by environmental tobacco smoke during pregnancy Table 2. Multiple linear regression models of CBCL by ETS exposure during pregnancy and metabolic gene polymorphisms. ETS= environmental tobacco smoke; CBCL= Child Behavior Checklist; Models adjusted for maternal education, family income, infant sex and birth weight, HOME score, and postnatal ETS exposure as reported on a questionnaire. * p-values < 0.05 Beta coefficient differs from the reference group without ETS exposure and with Infant gene CYP1A1 MspI (TT) + Infant gene CYP1A1 Ile462Val (Ile/Ile) * p-values < 0.05 Figure 1. Multiple linear regression models of CBCL by ETS exposure during pregnancy and both metabolic gene polymorphisms Conclusions In conclusion, our results support that prenatal ETS exposure may be associated with adverse behavioral development in early childhood and such relation could be modified by metabolic gene polymorphisms. Furthermore, infant genes appeared to have greater effects than maternal genes, and infant phase I genes, CYP1A1 MspI and CYP1A1 Ile462Val, played a more important role than the infant phase II genes studied. Corresponding author’s e-mail: pchen@ntu.edu.tw; First author’s e-mail: d94841007@ntu.edu.tw OMIH