Maternal And Paternal Environmental Risk Factors, Metabolizing GSTM1and GSTT1Polymorphisms And Their Interactions In Congenital Heart Disease

Congenital heart disease (CHD) is one of the most common birth defects throughout the world. The etiology of it is still unknown. Generally, most CHDs are thought to have a multifactorial origin, with interaction of genetic and environmental exposures. Studies have found that the effect of environmental factors might be modified by the metabolising enzymes genes which are responsible for the detoxification of toxicant agents, contributing to an increased susceptibility or resistance to cardiac teratogenesis. However, few epidemiological studies have paid attention to the difference of genetic susceptibility to environmental factors. Fourthmore, a case-control study generally depends on the collection of retrospective data, thus introducing the possibility of recall bias. People who have a disease may be more likely to remember exposures more readily than those without the disease. All above mentioned reasons could lead to different conclusions between different studies.Given this background, in the present study, we used matched case-control design to examine the association between the environmental risk factors of parents and CHD risk and to explore the modification effect of genetic susceptibility in children and their mothers who lacked the genetic capacity to produce the GSTM1and GSTT1enzymes. In addition, we chose patients of other birth defects as another control group to assess the impact of recall bias. Our objective here was to improve the quality and the credibility of the results, and to provide the evidence for further prospective study and personalized prevention of CHDs.Prat Ⅰ A Meta-analysis on Risk Factors of Congenital Heart Disease in Chinese PeopleObjectivesTo explore the risk factors of congenital heart disease (CHD) in Chinese people.Methods Published case-control studies concerning risk factors and CHD in Chinese people were systemically searched from January1993to February2013. Stata12.0software was used for Meta analysis and calculating OR and95%CI.ResultsA tota of19case-control studies including4769cases of congenital heart disease and6720controls were selected for meta-analysis. The pooled OR values of single-factor analysis were as follows:maternal exposure to chemieal toxic substances (OR=3.34,95%CI:2.62-4.25), having a fever during the first trimester of pregnancy (OR=3.64,95%CI:2.19-6.04), with history of spontaneous abortion (OR=3.03,95%CI:1.14-8.03), taking antibiotics during the first trimester (OR=2.49,95%CI:1.80-3.45). mental stimulation (OR=2.26,95%CI:1.66-3.06), maternal exposure to noise during the first trimester (OR=2.15,95%CI:1.34-3.43), mother with a history of catching a cold (OR=2.09,95%CI:1.67-2.63), history of adverse pregnancy outcomes (OR=1.81,95%CI:1.44-2.29), maternal passive smoking during the first trimester (OR=1.69,95%CI:1.11-2.57), taking analgesic and antipyretic drug during the first trimester (OR=2.52,95%CI:0.68-9.28), maternal exposure to pets during the first trimester (OR=2.30,95%CI:0.31-16.84), paternal smoking (OR=1.38,95%CI:0.94-2.02); The pooled OR values of multiple-factor analysis were as follows:mother with a history of catching a cold during the first trimester (OR=3.56,95%CI:1.93-6.55), mental stimulation (OR=2.69,95%CI:1.38-5.22), exposure to chemieal toxic substances (OR=2.61,95%CI:1.96-3.46)、history of adverse pregnancy outcomes (OR=1.76,95%CI:1.37-2.26).ConclusionsMaternal exposure to chemieal toxic substances during the first trimester, having a fever during the first trimester, with history of spontaneous abortion, history of adverse pregnancy outcomes, taking antibiotics during the first trimester, mental stimulation, maternal exposure to noise during the first trimester, mother with a history of catching a cold during the first trimester and maternal passive smoking during the first trimester are the risk factors for congenital heart disease in Chinese population. However, the relationship between congenital heart disease and maternal taking analgesic and antipyretic drug during the first trimester, maternal exposure to pets during the first trimester, paternal smoking should be further studied. Prat II Maternal and Paternal Environmental Risk Factors in Congenital Heart DiseaseObjectivesThe aim of this study is to explore the effect of maternal and paternal environmental risk factors on congenital heart disease in infants.MethodsA hospital-based paired case-control study (1:1) was conducted from October2011to January2013,204parents of0-7year’s old children with isolated CHD and204parents of children without any congenital malformations were invited to participate. The matching criteria for the controls were:1) with the same sex;2) with an age difference of less than8months. Both case and control parents completed a structured questionnaire on the demographic, preconceptional, and lifestyle exposures. Logistic regression was used to assess the association between maternal and paternal environmental exposure and congenital heart disease in their infants.ResultsA total of204CHD cases were included in the studies, which were comprised of94cases of VSD(46.08%)、26cases of ASD(12.75%)、25cases of complicated CHD(12.25%)、25cases of other simple CHD(12.25%)、24cases of PDA(11.76%)、10cases of F4(4.90%). Multivariate logistic regression analysis at the0.05significance level showed that the risk factors of CHD included:history of adverse pregnancy outcomes (OR=3.06), maternal exposure to pesticides during the first trimester of pregnancy (OR=3.57), maternal exposure to pets during the first trimester of pregnancy (OR=4.86), maternal passive smoking within3months prior to pregnancy (OR=2.16) and during the first trimester of pregnancy (OR=2.41), mother with a history of catching a cold (OR=2.19), having a fever (OR=2.20) and taking analgesic and antipyretic drug (OR=2.78) during the first trimester, living in a house renovated in past3years during the first trimester (OR=2.57), maternal residential proximity to industrial facilities (OR=2.22), high total stress score (>375) of life events during pregnancy (OR=2.18), paternal exposure to pesticides (OR=2.25) and paternal passive smoking (OR=1.79) within3months prior to pregnancy. In addition, maternal intake frequency of meat, poultry and fish≥3times/week (OR=0.55), intake frequency of animal offal≥3times/week (OR=0.37), folic acid supplementation (OR=0.38) and doing pre-pregnancy checkups (OR=0.50) were protective factors of CHD. ConclusionsAvoiding or reducing the exposure of environmental risk factors above, strengthening pre-pregnancy checkups and folic acid supplementation might help to reduce the risk of congenital heart disease.Prat Ⅲ Assessment for Recall Bias of Selected Environmental Risk Factors in this Case-control StudyObjectivesTo assess the impact of possible recall bias of selected environmental risk factors in Prat II.MethodsA paired case-control study (1:1) was carried out in the same hospital. A total of176parents of children with other birth defects except for congenital heart disease were invited to participate. The matching criteria for the defect control were the same sex and an age difference of less than8months with cases. Logistic regression analyses were used to calculate the odds ratio of each variable. The recall bias was assessed by comparing the difference of two odds ratio between case group compared with two control groups respectively.Results(1) A total of16variables were included in the analyses. A slightly elevated odds ratio was found in maternal passive smoking within3months prior to pregnancy, passive smoking during the first trimester of pregnancy and living in a house renovated in past3years during the first trimester when cases compared with control group2.(2) A slightly decreased but still statistically significant odds ratio was found in mother with a history of adverse pregnancy outcomes, maternal exposure to pesticides during the first trimester of pregnancy, maternal exposure to pets during the first trimester of pregnancy, mother with a history of catching a cold, having a fever and taking analgesic and antipyretic drug during the first trimester, intake frequency of meat, poultry and fish, intake frequency of animal offa, folic acid supplementation, doing pre-pregnancy checkups and paternal passive smoking within3months prior to pregnancy.(3) The association between CHD and maternal total stress score of life events during pregnancy (OR1=2.20,95%CI=1.04-4.64; OR2=1.31,95%CI=0.69-2.51) and paternal exposure to pesticides(OR1=2.42,95%CI=1.23-4.74; OR2=1.22,95%CI=0.76-2.95) were no longer statistically significant.ConclusionsFurther studies are necessary in order to conclude the association between maternal total stress score of life events during pregnancy, paternal exposure to pesticides and CHD risks.Prat IV GSTM1and GSTT1Gene Polymorphisms and Susceptibility to Congenital Heart DiseaseObjectivesTo explore the association between mother and childen’s GSTM1and GSTT1gene polymorphisms and susceptibility to congenital heart disease.MethodsNon-anticoagulant blood of children and oral mucosal epithelial cells of mothers were collected. Genomic DNA was extracted. The GSTM1and GSTT1genotypes were determined using a polymerase chain reaction approach with the albumin gene as the internal control to distinguish the null genotypes from aborted polymerase chain reaction.Results(1) The analysis of maternal single genotypes showed that:the frequency of GSTM1null genotype was55.3%and51.0%in mothers of case and control group respectively, but the difference was not statistically signifieant (P=0.54,OR=1.19,95%CI=0.68-2.08). The frequency of the GSTT1null genotype was53.4%and41.7%in mothers of case and control group respectively, but difference was not statistically signifieant(P=0.10,OR=1.60,95%CI=0.92-2.81).(2) The combined analysis of maternal genotypes showed that:the frequency of combined null GSTs in mothers of case group (34.0%) was higher than mothers of control group (19.8%), and the difference was statistically signifieant (P=0.03). The risk for CHD in mothers carrying both GSTM1null and GSTT1null genotypes was signifieantly higher than mothers carrying both GSTM1and GSTT1nonnull genotypes (P<0.05,OR=1.86,95%CI=1.02-3.38).(3) The analysis of children single genotypes showed that:he frequency of GSTM1null genotype was52.2%and47.8%in case and control group respectively, but difference was not statistically signifieant(P=0.40, OR=1.19,95%CI=0.79-1.80). The frequency of the GSTT1null genotype was53.9%and52.2%in case and control group respectively, but difference was not statistically signifieant(P=0.75, OR=1.07,95%CI=0.71-1.62). The distribution of either GSTM1or GSTT1genotype between boys and girls did not have signifieant differences(P>0.05).(4) The frequency of carrying both GSTM1null and GSTT1null genotypes was higher in case group (31.1%) than in control group (24.2%), but difference was not statistically signifieant (P=0.14, OR=1.42,95%CI=0.89-2.25).ConclusionsMothers carrying both GSTM1null and GSTT1null genotypes have an increase risk for their child with CHD.Prat V Interactions between Polymorphisms of GSTMl and GSTTl and Environmental Risk Factors in Congenital Heart DiseaseObjectivesTo evaluate the interactions between polymorphisms of GSTM1and GSTT1and environmental risk factors in CHD.MethodsWe used three measures of biological interaction presented by Rothman:RERI, the relative excess risk due to interaction; AP, the attributable proportion due to interaction; and S, the synergy index. If there is no biological interaction, the95%confidence intervals of RERI and AP should not included0and the95%confidence intervals of S should not included1.ResultsA total of5variables entered in the present analyses, incluing maternal passive smoking within3months prior to pregnancy, maternal passive smoking during the first trimester of pregnancy, taking analgesic and antipyretic drug during the first trimester, living in a house renovated in past3years during the first trimester and maternal residential proximity to industrial facilities.A positive additive interaction existed between children’s combined null GSTs genotypes and5variables above. Furthermore, the additive interaction between children’s combined null GSTs genotypes and maternal taking analgesic and antipyretic drug during the first trimester (RERI=3.65, AP=50%, S=2.36), maternal residential proximity to industrial facilities (RERI=3.37, AP=61%, S=3.98) were statistically significant.ConclusionsA significant interaction was found between combined null GSTs in children and maternal taking analgesic and antipyretic drug during the first trimester, maternal residential proximity to industrial facilities.