[Case-control study on the association between four single nucleotide polymorphisms in folate metabolism way and the risk of congenital heart disease]. 
To investigate the association between single nucleotide polymorphisms( SNPs) of 5, 10-methylenetetrahydrofolate reductase( MTHFR) C677T, A1298C, methionine synthase( MS) A2756G, methionine synthase reductase( MTRR) A66G and the risk of congenital heart disease( CHD).  By restricting the corresponding conditions, a case-control study was performed.  We collected 200 congenital heart disease children as case group and 200 normal children as control group admitted to the Department of cardiac surgery, Children 's Hospital of Hebei Province from January 2016 to April 2017.  The genotype of MTHFR C677T, A1298C, MS A2756G, and MTRR A66G polymorphisms were detected by Sanger sequencing followed PCR.  Assessing the relationships between 4 SNPs and the risk of whole CHD and different types of CHD.  The mutant allete T of MTHFR C677T had contribute to the risk of developing CHD( OR = 2.  47, 95% CI 1.  86-3.  29, P < 0.  001).  Compared with the wild CC genotype, heterozygosity CT had a higher risk of CHD( OR = 2.  32, 95% CI 1.  35-3.  98, P < 0.  05), the homozygous mutant genotype TT increased the risk of CHD by 5.  37( 95% CI 3.  01-9.  60, P < 0.  001).  The mutant allele C of MTHFR A1298C was a protective factor for CHD( OR = 0.  53, 95% CI 0.  36-0.  77, P < 0.  05).  Compared with the wild AA genotype, heterozygosity AC had a lower risk of CHD( OR = 0.  41, 95% CI0.  26-0.  64, P < 0.  001).  After typing, the allele frequencies and genotypes frequencies of the above two SNPs were still statistically significant( P < 0.  05).  The combined genotype analysis of the above two SNPs showed that: compared with the CC/AA genotype, individuals with CT/AA had a higher risk of CHD( OR = 4.  65, 95% CI 2.  16-10.  02), the TT/AA type increased to 7.  05( 95% CI 3.  37-14.  79).  However, the polymorphisms of MS A2756G and MTRR A66G had no significant relationship with the risk of CHD( P > 0.  05).  The mutant allele T of MTHFR C677T may be a risk factor for CHD and the mutant allele C of A1298C may be a protective factor for CHD.  These two SNPs may have a joint effect on the occurrence of CHD.