Association Between Intrauterine PAHs Exposure, Genetic Polymorphisms Of Newborn GSTM1/XPD751 And Birth Outcomes

Objective To know more about the impact of prenatal exposure of polycyclic aromatic hydrocarbons(PAHs) on the birth outcome situations of newborns in Tai-yuan by epidemiology investigation and biological sample detection. To explore the related factors of PAHs exposure level of pregant and fetus and the newborns birth outcomes. Try to find out the interactions of GSTM1, XPD751 polymorphisms and prenatal exposure to PAHs on birth outcomes. This was designed to explore the association between GSTM1, XPD polymorphisms and fetal birth outcomes, and try to provide approach for the biological mechanism study between them. In a word, this study was designed to provide a scientific references for selecting susceptible population, controlling environmental pollution and conducting researches related to prevent the prenatal exposure to PAHs.Methods1. To indentify Taiyuan as the research field according to the past air monitoring data and related documents at home and aborad.2. The basic information, including information on the demography, pregnancy and childbearing history, personal life style, residential and environmental exposures, diet habits, family disease history and spouse informations, was collected by a detailed and validated questionnaire. The data about birth outcome indexes was amassed from hospital.3. Sampling and measuring3.1 Seven PAHs in gravida peripheral serum and umbilical cord serum were detected by High Performance Liquid Chromatography (HPLC).3.2 The genotyping of newborns GSTM1 and XPD751 was using techniques based on PCR or RFLP-PCR.Results1. The category of energy, if have a exhaust system in kitchen, cooking frequencies during pregnancy and if have ventilation habit in living room were the independent factors related to gravida serum PAHs level (p<0.05).2. The multiple linear regressions model results showed that cooking frequencies and ventilation habit were the independent factors to mother serum PAHs level after controlling the confounding variables in multiple linear regression models.3. GSTM1 may play a modification role in newborns PAHs exposure levels.4. Birth weight and length were significantly related with mothers PAHs level, which showed significant difference among different PAHs exposure levels(P<0.05).5. Genetically determined differences in GSTM1 and XPD751 genotypes modified the association between PAHs exposure and birth outcomes.PAHs exposure-gene interactions analysis indicated:The interactions of mother PAHs exposure level and GSTM1, XPD751 genetic polymorphisms both had significant difference in birth weight and length(all P<0.05). The interactions of newborns PAHs exposure level and GSTM1 genetic polymorphism had significant difference in birth weight (P=0.026).GSTM1, XPD751 interactions analysis indicated:The interactions of combined GSTM1 and XPD751 genotype had significant difference in birth weight (P=0.007). A significant reduction in birth weight was found among neonates with GSTM1 absent genotype and XPD751Gln mutant genotype(P=0.004), and this was also similar in birth height(P=0.04), and futher the birth height of newborns who had GSTM1 present genotype with XPD751 mutant allele was shorter 1.16cm than the ones who had XPD751 wild genotype(P=0.02), whereas the gene-gene interactive effect of GSTM1 and XPD751 on birth length was not statiscally significant(F=1.718, P=0.064). Conclusions1. Cooking frequencies after pregnancy and ventilation habit were the independent factors to mothers serum PAHs level, and indicated that indoor air PAHs pollutions were the important factors of pregnant women exposure to PAHs.2. GSTM1 may play a modification role in newborns PAHs exposure levels.3. Mothers PAHs level was significantly related with newborns birth weight and birth length.3. The interactions of mother PAHs exposure level and GSTM1, XPD751 genetic polymorphism both had significant difference in birth weight and length. The interactions of newborns PAHs exposure level and GSTM1 genetic polymorphism had significant difference in birth weight. The interactions of newborns GSTM1 and XPD751 had significant difference in birth weight. High PAHs exposure, GSTM1 absent genotype and XPD751 mutant genotype maybe the risk factors of newborns birth outcomes, and the association supported regarding the importance of futher assessing the role of interactions of GSTM1, XPD751 and in-utero PAHs exposure in relation to fetal birth outcomes.