title: Association of SNPs in genes involved in folate metabolism with the risk of congenital heart disease.
abstract: 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.
authors.affiliation: Center for Reproduction and Genetics, Nanjing Medical University Affiliated Suzhou Hospital , Suzhou, Jiangsu Province 215002 , China.
authors.forename: Benjing
authors.initials: B
authors.lastname: Wang
authors.forename: Minjuan
authors.initials: M
authors.lastname: Liu
authors.forename: Wenhua
authors.initials: W
authors.lastname: Yan
authors.forename: Jun
authors.initials: J
authors.lastname: Mao
authors.forename: Dong
authors.initials: D
authors.lastname: Jiang
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
mesh_terms: D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005287:Ferredoxin-NADP Reductase / Q000235:genetics; D005492:Folic Acid / Q000378:metabolism*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006330:Heart Defects, Congenital / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D051150:Methionine Sulfoxide Reductases / Q000235:genetics; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008840:Microfilament Proteins; D051267:NF-E2-Related Factor 2 / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D058978:Reduced Folate Carrier Protein / Q000235:genetics; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics
chemical_list: D008840:Microfilament Proteins; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D058978:Reduced Folate Carrier Protein; C548699:SLC19A1 protein, human; D014157:Transcription Factors; D005492:Folic Acid; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C120376:MSRB2 protein, human; D051150:Methionine Sulfoxide Reductases