Association Of Methylenetetrahydrofolate Reductase,Methionine Synthase Reductase Gene Polymorphisms And Folic Acid Supplyment With Fetal Congenital Heart Disease

Congenital heart disease(CHD)is the most common birth defect and also a leading cause of death from Congenital deformities in the newborn and infants.This has caused serious economic,mental and medical burdens to individuals,families and society,and has become a major issue affecting children,s health and the quality of life of the population.At present,most studies have shown that CHD is caused by both genetic and environmental factors,but the specific pathogenesis and mechanism are still controversial.Folate is the general term of a group of compounds,which is the essential B family vitamin for the human body.It can not be synthesized by human body itself,but can only be obtained from the diet.Studies have shown that folate plays an important role in embryonic development,including the development of the cardiovascular system.With the development of molecular biology,the susceptibility of genes in the folate metabolism pathway is also well known.5-10-Methylenetetrahydrofolate reductase(MTHFR)and methionine synthase reductase(MTRR)are key enzymes in folate metabolism and play an important role in the methionine cycle.The mutations of 677C?T and 1298A?C of MTHFR gene and 66A?G of MTRR gene decrease the activity of corresponding enzymes and lead to the disorder of folate metabolism,which hinders the methionine cycle.On the one hand,it affects the methylation reaction in the body and affects the metabolic growth of cells;on the other hand,it leads to the metabolic disorder of Homocysteine(Hcy)in the body,which makes the Hcy increase.The abnormal accumulation of Hcy is a risk factor for the abnormal development of cardiovascular diseases.Therefore,the mutation of folate metabolism key enzyme gene leads to decreased enzyme activity,abnormal DNA synthesis and repair,abnormal neural crest development in embryos,and then the formation of CHD.However,there is still doubt about the relationship between folate metabolism enzyme gene polymorphism and CHD and how to properly take folic acid during pregnancy to prevent the occurrence of CHD.Therefore,this study intends to further explore the correlation between folate metabolism and CHD from the above two aspects,in order to provide a new basis for the prevention of CHD by taking folic acid during pregnancy.ObjectiveTo analyze the relationship between maternal folic acid metabolism key enzyme gene MTHFR,MTRR polymorphism,folic acid supplementation during pregnancy and fetal congenital heart disease.Material and methodsPregnant women who were examined in the third affiliated hospital of zhengzhou university from June 2017 to October 2018 were selected.Among them,pregnant women who were diagnosed by echocardiography as fetal congenital heart disease were in the case group,while those who were diagnosed by echocardiography as non-fetal congenital heart disease were in the control group.An interview questionnaire survey was conducted in the two groups.The survey included the general condition of the fetus(the gestational age and the type of congenital heart disease),the general condition of the mother(age,ethnicity,permanent residence,education,height,pre-pregnancy weight,blood pressure,past history,marriage History,family history,history of smoking and drinking,history of exposure to radioactive materials and chemicals,folic acid supplementation,history of medication in early pregnancy,etc.).After the investigation,oral mucosal epithelial cells of the subjects were collected for MTHFR gene C677 T,A1298C and MTRR gene A66 G gene detection,meanwhile,venous blood of pregnant women was sampled to determine homocysteine concentration.Pregnancy outcomes of pregnant women were followed up until delivery.The collected data was input into the SPSS 21.0 data window for statistical analysis.All the test level was ?=0.05,P < 0.05 was considered statistically significant.Results1.Allele frequencies of MTHFR677 T and MTRR66 G in the case group were higher than those in the control group(P < 0.05).The genotypes of MTHFRTT,MTRRAG and GG in the case group were higher than those in the control group(P < 0.05).The genotype frequencies of MTHFRCT,MTRRGG,MTHFRTT and MTRRAG in the case group were higher than those in the control group(P < 0.05).2.In the case group,55patients(55.0%)had regular oral administration of folic acid during pregnancy,and 143patients(71.5%)had regular oral administration of folic acid in the control group.According to the two-class logistic analysis,regulating folic acid supplementation is a protective factor for congenital heart disease,which is conducive to reducing the incidence of congenital heart disease(OR=0.487,95%CI=0.296-0.803,p<0.05).3.The mean blood Hcy concentration in the case group(9.79±3.69?mol/L)was higher than that in the control group(7.55±2.23?mol/L),and the difference between the two groups was statistically significant(P < 0.05).4.In the regular folic acid supplementation group,there was no statistically significant difference in MTHFR677 CT and TT genotypes,MTRR66 AG and GG genotypes in the two groups(P > 0.05).In the irregular folic acid supplementation group,the MTHFR677 CT and TT genotypes,MTRR66 AG and GG in the case group were significantly higher than those in the control group(P < 0.05).Conclusions1.TMTHFR677C?T and MTRR66A?G increases the risk of congenital heart disease in offspring,moreover,the combination of the two genes mutation can increase the risk of disease.2.Regular folic acid supplementation can prevent congenital heart disease caused by folate metabolism disorder.