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Association Of Maternal Folic Acid Intake And RFC1 Gene Polymorphism With Congenital Heart Disease In Offspring

Posted on:2023-08-01Degree:MasterType:Thesis
Country:ChinaCandidate:J Q LiFull Text:PDF
GTID:2544307070990529Subject:Epidemiology and Health Statistics
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Objective1.To evaluate the influence of whether mothers take folic acid during periconceptional period and the time when they start taking folic acid on the occurrence of congenital heart disease(CHD)in their offspring,so as to provide scientific and effective health guidance for women of childbearing age to take folic acid.2.To evaluate the correlation between maternal reduced folate carrier gene(RFC1)polymorphism and offspring CHD,so as to provide a new target for the study of CHD susceptibility population.3.To evaluate the interaction between maternal folic acid intake and RFC1 gene polymorphism on offspring CHD,and provide scientific basis for individual prevention of CHD.MethodsThis study adopted a hospital-based case-control study design.The case group consisted of mothers of patients with simple CHD who visited the Cardiothoracic Surgery department of Hunan Children’s Hospital from May 2018 to December 2020,and the control group consisted of mothers of hospitalized children without any congenital malformation during the same period.Exposure indicators of interest include maternal periconceptional folic acid use and RFC1 gene polymorphism.In this study,NCBI and HapMap databases were searched,and r2<0.8 and minor allele frequency(MAF)≥10%were used to select the backup locus for this gene.Finally,six loci(rs10483080,rs2236484,rs3788190,rs3788189,rs 12483377 and rs2330183)were screened as standby loci.The ratio and composition of counting data between the two groups were described,and Pearson Chi-square test or Wilcoxon rank sum test was used for comparison.Logistic regression analysis was used to calculate the odds ratio(OR)and 95%confidence interval(CI)of unadjusted and adjusted factors,and to evaluate the association between exposure factors and the risk of CHD.The additive interaction between RFC1 gene and periconceptional folic acid intake was evaluated by cross-sectional analysis.Logistic regression analysis was used to evaluate the multiplicative interaction between RFC1 gene and periconceptional folic acid intake.In addition,based on the interaction analysis,the separate effect of RFC1 genetic variation on the risk of CHD was further evaluated by stratification according to folic acid intake.Results1.Multivariate logistic regression was used to control for confounding factors and showed that maternal failure to take folic acid during pregnancy significantly increased the risk of CHD in offspring compared with mothers taking folic acid during periconceptional(OR=2.04,95%CI:1.42-2.93).Starting folic acid in early pregnancy(OR=1.90,95%CI:1.43-2.54)and starting folic acid in middle and late pregnancy(OR=8.92,95%CI:4.20-18.97)significantly increased the risk of CHD in offspring compared with starting folic acid before pregnancy.2.The polymorphisms of rs2236484 and rs2330183 in RFC1 gene were associated with the risk of CHD in offspring after multiple logistic regression was used to control for confounding factors.At rs2236484,AG(OR=1.79;95%CI:1.33-2.39)and GG(OR=1.64;95%CI:1.15-2.35)genotype mothers significantly increased the risk of CHD in their offspring compared with AA genotype mothers;Dominant model of this locus(OR=1.74;95%CI:1.32-2.30)and additive model(OR=1.31;95%CI:1.10-1.57)were associated with a risk of CHD.At locus rs2330183,maternal CT genotype significantly increased the risk of offspring CHD compared with CC genotype(OR=1.54;95%CI:1.14-2.09);The dominant model of this locus was associated with the risk of CHD(OR=1.46;95%CI:1.10-1.93).3.Cross-sectional analysis showed that the genetic variation of rs2236484 in maternal RFC1 gene had a positive additive interaction with the occurrence of CHD in offspring without perinatal folic acid(RERI=4.35,95%CI:1.53-7.18;AP=0.73,95%CI:0.57-0.90;S=8.46,95%CI:2.07-34.55).Logistic regression analysis showed that rs2236484(OR=3.72,95%CI:2.27-6.11)and rs3788190(OR=1.93,95%CI:1.20-3.09),rs3788189(OR=1.55,95%CI:1.03-2.33)and rs2330183(OR=1.91,95%CI:1.18-3.08)had synergistic multiplicative interactions with the absence of folic acid during periconceptional.Stratified by folic acid use,the risk of offspring CHD due to genetic variation in the RFC1 gene was significantly higher in mothers who did not take folic acid than in mothers who took folic acid.Conclusions1.Whether or not to take folic acid in periconceptional period and the time of starting to take folic acid in periconceptional period are associated with the risk of CHD in offspring.2.Polymorphism of rs2236484 and rs2330183 in RFC1 gene is associated with the risk of CHD in offspring.3.There is an interaction between maternal RFC1 gene and periconceptional folic acid supplementation in the risk of CHD in offspring.Among mothers with mutations in this gene locus,the risk of CHD in offspring is reduced in mothers with periconceptional folic acid supplementation.
Keywords/Search Tags:Folic acid, RFC1, Gene polymorphism, Congenital heart disease, Interaction
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