The Correlation Of MTHFR C677T Gene Polymorphism With Fetal CHD And Chromosome Abnormality

Objective To analyse the distribution of MTHFR C677T gene polymorphism in pregnant women,to discuss the correlation of MTHFR C677T gene polymorphism with fetal CHD and chromosome abnormality.Methods We selected the healthy single-fetal prengnant women who underwent the detection of the MTHFR C677T gene polymorphism in Prenatal Diagnostic Center of Ningxia Medical University General Hospital from January 2019 to December 2020 as the research targets.According to the inclusion and exclusion criteria,278 cases of fetal cardiac structural abnormality revealed by prenatal ultrasound follow-up were included in the fetal CHD group;91 cases of fetal chromosomal abnormality revealed by invasive prenatal diagnosis were included in the fetal chromosomal abnormality group;275 cases of normal fetuses revealed by prenatal ultrasound and invasive prenatal diagnosis were included in the control group.Stratification:1.According to the types of fetal CHD,fetal CHD group（Case A）were divided into:septal defect CHD group（Case A₁）,obstructive defect CHD group（Case A₂）,complex cardiovascular malformation group（Case A₃）.2.According to the types of fetal chromosomal abnormalities,the fetal chromosomal abnormality group（Case B）were divided into:fetal chromosomal aneuploidy group（Case B₁）,fetal pCNV group（Case B₂）.The fetal chromosomal aneuploidy group were further divided into:fetal trisomy 21 syndrome group(Case B_1a),fetal the other chromosomal aneuploidy group(Case B_1b).The distribution of MTHFR C677T gene polymorphism were collected and compared between those cases groups and the control group.Results 1.The frequencies of the MTHFR 677 CT,TT genotypes and T allele in fetal CHD group were significantly higher than in control group（P<0.05）,the frequencies of the CC genotype in fetal CHD group were significantly lower than in control group（P<0.05）.Logistic regression analysis showed that the pregnant women with CT and TT genotypes increased the risk of fetuses suffering from the CHD is 2.443 times（95%CI:1.624-3.677,P=0.000）and 3.051 times（95%CI:1.877-4.958,P=0.000）higher than those with CC genotype.The pregnant women with mutant allele T increased the risk of fetuses suffering from the CHD is 1.783 times（95%CI:1.405-2.264,P=0.000）higher than those with allele C.In the stratified study,the frequencies of the CT,TT genotypes and T allele in septal defect CHD group were significantly higher than in control group（P<0.05）,the frequencies of the CC genotype in septal defect CHD group were significantly lower than in control group（P<0.05）.Logistic regression analysis showed that the pregnant women with CT and TT genotypes increased the risk of fetuses suffering from the septal defect CHD is 2.316 times（95%CI:1.442-3.719,P=0.001）and 2.779 times（95%CI:1.590-4.858,P=0.000）higher than those with CC genotype.The pregnant women with mutant allele T increased the risk of fetuses suffering from the septal defect CHD is 1.709 times（95%CI:1.300-2.246,P=0.000）higher than those with allele C.There were no significant difference for the frequencies of CC,CT,TT genotypes and T allele between the obstructive defect CHD group and the control group（P>0.05）.The frequencies of the CT,TT genotypes and T allele in fetal complex cardiovascular malformation group were significantly higher than in control group（P<0.05）,the frequencies of the CC genotype in fetal complex cardiovascular malformation group were significantly lower than in control group（P<0.05）.Logistic regression analysis showed that the pregnant women with CT and TT genotypes increased the risk of fetuses suffering from the complex cardiovascular malformation is 3.187 times（95%CI:1.669-6.086,P=0.000）and3.900 times（95%CI:1.876-8.108,P=0.000）higher than those with CC genotype.The pregnant women with mutant allele T increased the risk of fetuses suffering from the complex cardiovascular malformation is 1.956 times（95%CI:1.393-2.745,P=0.000）higher than those with allele C.2.The frequencies of the MTHFR 677 CT genotype and T allele in fetal chromosomal abnormality group were significantly higher than in control group（P<0.05）,the frequencies of the CC genotype in fetal chromosomal abnormality group were significantly lower than in control group（P<0.05）.Logistic regression analysis showed that the pregnant women with CT and TT genotypes increased the risk of fetuses suffering from the chromosomal abnormality is2.779 times（95%CI:1.518-5.088,P=0.001）and 2.471 times（95%CI:1.192-5.122,P=0.015）higher than those with CC genotype.The pregnant women with mutant allele T increased the risk of fetuses suffering from the chromosomal abnormality is 1.602times（95%CI:1.144-2.245,P=0.006）higher than those with allele C.In the stratified study,the frequencies of the CT genotype and T allele in fetal chromosome aneuploidy group were significantly higher than in control group（P<0.05）,the frequencies of the CC genotype in fetal chromosome aneuploidy group were significantly lower than in control group（P<0.05）.Logistic regression analysis showed that the pregnant women with CT and TT genotypes increased the risk of fetuses suffering from the chromosome aneuploidy is 2.692 times（95%CI:1.366-5.305,P=0.004）and 2.746 times（95%CI:1.238-6.092,P=0.013）higher than those with CC genotype.The pregnant women with mutant allele T increased the risk of fetuses suffering from the chromosome aneuploidy is 1.682 times（95%CI:1.158-2.442,P=0.006）higher than those with allele C.The frequencies of the CT genotype and T allele in fetal trisomy 21 syndrome group were significantly higher than in control group（P<0.05）,the frequencies of the CC genotype in fetal trisomy 21 syndrome group were significantly lower than in control group（P<0.05）.Logistic regression analysis showed that the pregnant women with CT and TT genotypes increased the risk of fetuses suffering from the trisomy 21syndrome is 4.375 times（95%CI:1.449-13.209,P=0.009）and 3.675 times（95%CI:1.028-13.136,P=0.045）higher than those with CC genotype.The pregnant women with mutant allele T increased the risk of fetuses suffering from the trisomy 21 syndrome is1.821 times（95%CI:1.074-3.090,P=0.026）higher than those with allele C.There were no significant difference for the frequencies of CC,CT,TT genotypes and T allele between the the other chromosome aneuploidy group and the control group（P>0.05）.The frequencies of the CT genotype in fetal pCNV group were significantly higher than in control group（P<0.05）.Logistic regression analysis showed that the pregnant women with CT and TT genotypes increased the risk of fetuses suffering from the pCNV is 3.062 times（95%CI:0.978～9.591,P=0.055）and 1.575 times（95%CI:0.340～7.305,P=0.562）higher than those with CC genotype.The pregnant women with mutant allele T increased the risk of fetuses suffering from the pCNV is 1.364 times（95%CI:0.727～2.558,P=0.334）higher than those with allele C.Conclusion 1.The mutation of the MTHFR C677T gene is associated with the septal defect CHD and complex cardiovascular malformation,which belongs to the fetal congenital heart disease.2.The mutation of the MTHFR C677T gene is associated with the fetal trisomy 21syndrome,which belongs to the fetal chromosome aneuploidy.3.There are no association between the mutation of the MTHFR C677T gene and the fetal pCNV.