| Purpose:To explore the association between maternal MTHFD1gene single nucleotide polymorphism(SNP)and congenital heart disease(CHD)in offspring.To explore the haplotypes of MTHFD1gene associated with CHD and to analyze the gene-gene interaction with risk of CHD in offspring.Methods:In this study,a hospital-based case-control study was used.Recruitment was conducted by the Hunan Children’s Hospital from May2018 to December 2020.Mothers of CHD children in the Department of Cardiothoracic Surgery were identified as the case group.Mothers of children in the Department of Child Healthcare who were admitted to the same hospital at the same time,excluding any malformities were selected as the control group.Basic information and exposure factors of subjects,as well as blood samples were collected.SNPs of MTHFD1 gene were detected with Massarray time-of-flight mass spectrometry.The cases and rate/ratio were used in qualitative data,the Chi-squared test was used to compare differences between the case and control group.Logistic regression combined with propensity score correction analysis was used to analyze the association between MTHFD1 gene SNPs and CHD,and unadjusted odds ratio(OR)and 95%confidence interval(CI),as well as adjusted OR and 95%CI in codominant,dominant,recessive,overdominant,additive genetic model were calculated.Online software SNPStats was used to select the best genetic model of each SNP.Haploview 4.2 and SHEsis software were used in the linkage disequilibrium analysis and haplotype analysis.Finally,generalized multifactor dimensionality reduction(GMDR)was used to analyze the gene-gene interaction.Results:(1)A total of 1423 subjects were included in this study,including 683 cases and 740 controls.Hardy-Weinberg equilibrium results showed that except for rs11849530,the other seven SNPs conformed to the Hardy-Weinberg equilibrium(P>0.05).(2)After adjusting for those confounding factors based on propensity score correction analysis,the results of multivariate logistic regression analysis demonstrated that maternal rs1950902 polymorphism was associated with a decreased risk of CHD in offspring(GG vs.AA:OR=0.55,95%CI:0.35-0.86;additive model:OR=0.77,95%CI:0.63-0.94).Maternal rs1256142 polymorphism was associated with an increased risk of CHD in offspring(GG vs.GA:OR=2.38,95%CI:1.68-3.37;GG vs.AA:OR=2.74,95%CI:1.84-4.10;dominant model:OR=2.49,95%CI:1.78-3.47;additive model:OR=1.64,95%CI:1.34-2.00).The polymorphisms of rs2236225,rs2236222,rs1256146,rs2236224 and rs34616731 were not associated with the occurrence of CHD.The results of propensity score correction analysis for adjusting confounding factors were consistent with those of traditional method for adjusting multiple confounding factors.(3)The frequency distribution of haplotype GGA of rs2236225-rs2236224-rs1256142 had a significant difference between the case and control group(χ~2=20.191,P<0.001),and haplotype GGA increased the risk of CHD in offspring(OR=1.41,95%CI:1.22-1.64).There was also a significant difference in the frequency distribution of haplotype GGG between the two groups(χ~2=40.572,P<0.001),but haplotype GGG decreased the risk of CHD in offspring(OR=0.55,95%CI:0.46-0.66).(4)The result of GMDR showed that the second-order interaction model composed of rs1950902-rs2236222-rs1256142was the best model(P=0.001).Conclusions:(1)Polymorphisms of rs1950902 and rs1256142 in maternal MTHFD1 gene are associated with the occurrence of CHD in offspring.AA genotype of rs1950902 is associated with a decreased risk of CHD.GA or AA genotype of rs1256142 is associated with an increased risk of CHD in offspring.(2)The haplotypes GGA and GGG of rs2236225-rs2236224-rs1256142 might be associated with the risk of CHD.Haplotype GGA increases the risk of CHD in offspring while haplotype GGG decreases the risk of CHD in offspring.(3)The gene-gene interaction might exist among rs1950902,rs2236222 and rs1256142,which may be related to the occurrence of CHD. |
PDF Full Text Request