Associations of CYP450 gene polymorphism and exposed to environmental risk factors with congenital heart disease:a case-control study

Objective To explore the effects of maternal environmental risk factor exposure and gene polymorphisms of cytochrome P450 (CYP450) on congenital heart disease (CHD) in infants,and to assess whether there is an interactive effect between maternal environmental risk factors and gene polymorphisms of CYP450 on CHD.Methods A hospital-based matched case-control study (1:1) was conducted from October 2011 to January 2013.A total of 160 children of 0-7 years old with isolated CHD (cases) and 160 children without any congenital malformations (controls) were recruited.Mothers of the cases and controls were interviewed to obtain information on demographic characteristics of the mother-baby pairs,as well as maternal toxicants exposures during the first trimester of pregnancy.The genotype of CYP450 was determined with polymerase chain reaction restricted fragment length polymorphism (PCR-RFLP).Univariate and multivariate logistic regression were used to assess the association between maternal environmental exposure and gene polymorphisms of CYP450 and the risk of CHD in their infants.Three indexes were used to evaluate the biological interactions between the CYP1A1 homozygous mutant type and CHD.Results The results of multivariate conditional logistic regression demonstrated that the offspring's homozygous mutant type of CYP1A1 rs1048943 was a protective factor for CHD (odds ratioOR=0.369,95% confidence intervalCI:0.138-0.986).Maternal usage of hair dyeing during 3 months before the pregnancy (adjusted odds ratioaOR=5.62,95%CI:1.401-22.541),exposed to passive smoking during 3 months before the pregnancy (aOR=2.511;95%CI:1.342-4.699) and during the first trimester (aOR=2.441,95%CI:1.306-4.561),living in a house decorated within past 3 years during the first trimester (aOR=4.159,95%CI:1.698-10.182),and taking analgesic or antipyretic drug during the first trimester (aOR=3.901,95%CI=1.271-11.971) were associated with an increased risk of CHD.The effects of environmental factors mentioned above on CHD could be attenuated when the infants carrying homozygous mutant type of CYP1A1 rs1048943,but the interactive effect indexes were of no statistical significance.Conclusion Carrying homozygous mutant type of CYP1A1 plays a protective role on the occurrence of CHD for offsprings.Avoiding or reducing maternal exposure to environmental risk factors before the pregnancy and during the first trimester might help to prevent the offspring from congenital heart disease.