title: Combined folate gene MTHFD and TC polymorphisms as maternal risk factors for Down syndrome in China.
abstract: We examined whether polymorphisms in the methylenetetrahydrofolate dehydrogenase (MTHFD) and transcobalamin (TC) genes, which are involved in folate metabolism, affect maternal risk for Down syndrome. We investigated 76 Down syndrome mothers and 115 control mothers from Bengbu, China. Genomic DNA was isolated from the peripheral lymphocytes. Polymerase chain reaction and restriction fragment length polymorphism were used to examine the polymorphisms of MTHFD G1958A and TC C776G. The frequencies of the polymorphic alleles were 24.3 and 19.1% for MTHFD 1958A, 53.9 and 54.2% for TC 776G, in the case and control groups, respectively. No significant differences were found between two groups in relation to either the allele or the genotype frequency for both polymorphisms. However, when gene-gene interactions between these two polymorphisms together with previous studied C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene were analyzed, the combined MTHFR 677CT/TT and MTHFD 1958AA/GA genotype was found to be significantly associated with the risk of having a Down syndrome child [odds ratio (OR) = 3.11; 95% confidence interval (95%CI) = 1.07-9.02]. In addition, the combined TC 776CG and MTHFR 677TT genotype increased the risk of having a child with Down syndrome 3.64-fold (OR = 3.64; 95%CI = 1.28-10.31). In conclusion, neither MTHFD G1958A nor TC C776G polymorphisms are an independent risk factor for Down syndrome. However, the combined MTHFD/MTHFR, TC/MTHFR genotypes play a role in the risk of bearing a Down syndrome child in the Chinese population.
authors.affiliation: Department of Cell Biology, Bengbu Medical College, Bengbu, China.
authors.forename: Y P
authors.initials: YP
authors.lastname: Liao
authors.affiliation: Department of Cell Biology, Bengbu Medical College, Bengbu, China.
authors.forename: D
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology, Bengbu Medical College, Bengbu, China.
authors.forename: W
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Cell Biology, Bengbu Medical College, Bengbu, China.
authors.forename: F M
authors.initials: FM
authors.lastname: Meng
authors.affiliation: Department of Cell Biology, Bengbu Medical College, Bengbu, China.
authors.forename: M S
authors.initials: MS
authors.lastname: Bao
authors.affiliation: The Central Laboratory, First Affiliated Hospital, Bengbu Medical College, Bengbu, China.
authors.forename: P
authors.initials: P
authors.lastname: Xiang
authors.affiliation: Department of Cell Biology, Bengbu Medical College, Bengbu, China ghoststories@sina.com.
authors.forename: C Q
authors.initials: CQ
authors.lastname: Liu
mesh_terms: D000328:Adult; D000619:Aminohydrolases / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D002648:Child; D002681:China; D004314:Down Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005492:Folic Acid / Q000235:genetics / Q000378:metabolism; D005574:Formate-Tetrahydrofolate Ligase / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000235:genetics*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D009097:Multienzyme Complexes / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014155:Transcobalamins / Q000235:genetics*
chemical_list: D009097:Multienzyme Complexes; D014155:Transcobalamins; C021836:formyl-methenyl-methylenetetrahydrofolate synthetase; D005492:Folic Acid; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008754:Methylenetetrahydrofolate Dehydrogenase (NADP); D000619:Aminohydrolases; D005574:Formate-Tetrahydrofolate Ligase