Objective: To investigate the association of 12 single nucleotide polymorphisms (SNPs) in folate metabolic genes with congenital heart disease (CHD).
Methods: A total of 160 children with CHD and 188 control children were enrolled. Twelve SNPs related to folate metabolism, including CBS-C699T, DHFR-c594 + 59del19, FOLH1-T1561C, CBS-C699T, DHFR-c594 + 59del19, GSTO1-C428T, MTHFD-G878A and -G1958A, MTHFR-C677T and -A1298C, MTR-A2756G, MTRR-A66G, NFE2L2-ins1 + C11108T, RFC1-G80A, TCN2-C776T and TYMS-1494del6, were genotyped by SNaPShot genotyping technology and confirmed by Sanger sequencing.
Results: There were two SNPs including NFE2L2-ins1 + C11108T and GST01-C428T and two compound mutants for (MTHFD-G1958A, MTHFR-C677T and MTR-A2756G) and (MTHFD-G1958A, RFC1-G80A and MTR-A2756G), which might increase the risk of CHD, and DHFR-c594 + 59del19 might decrease the risk of CHD. The CT genotype of NFE2L2-ins1 + C11108T, OR = 2.15 (95% CI = [1.07, 4.32], p < 0.05). The CT + TT genotype of NFE2L2-ins1 + C11108T, OR = 1.98 (95% CI = [1.00, 3.93], p < 0.05). The TT genotype of GST01-C428T, OR = 3.49, (95CI% = [1.06, 11.5], p < 0.05). The GG genotype of DHFR-c594 + 59del19, OR = 0.46 (CI% = [0.24, 0.87], p < 0.05). The AG + GG genotype of DHFR-c594 + 59del19, OR = 0.53 (CI% = [0.29, 0.96], p < 0.05). The ratios of the two compound mutants for (MTHFD-G1958A, MTHFR-C677T and MTR-A2756G) and (MTHFD-G1958A, RFC1-G80A and MTR-A2756G) in CHD are higher than that in control, p < 0.05 (OR = 2.968, 95% CI = [1.022, 8.613]).
Conclusions: The CT genotype of NFE2L2-ins1 + C11108T and the TT genotype of GST01-C428T are susceptible factors for CHD. The AG, GG and (AG + GG) genotypes of DHFR-c594 + 59del19 are protective genotypes for CHD. Compound mutants for (MTHFD-G1958A, MTHFR-C677T and MTR-A2756G) and (MTHFD-G1958A, RFC1-G80A and MTR-A2756G) may increase the risk of CHD.