The ten strongest association signals (p-value range: 0.0003-0.0023) were found in nine genes (MFTC, CDKN2A, ADA, PEMT, CUBN, GART, DNMT3A, MTHFD1 and T (Brachyury)) and included the known NTD risk factor MTHFD1 R653Q (rs2236225).
In summary, our meta-analysis strongly suggests that the MTHFD1 G1958A polymorphism might be associated with maternal risk for NTDs in Caucasian populations.
The haplotype GGGG, which consists of 4 SNPs (rs2236225, rs2236224, rs1256146, and rs6573559), is also associated with risk of NTDs (P value=0.0438, OR=0.7180, 95% CI=0.5214-0.9888).
The polymorphism of SNP loci rs1956545 and rs56811449 as well as a haplotype in MTHFD1 gene could serve as an indicator for the occurrence of NTDs in Chinese population and some specific genotypes of the loci may have lower risk of developing NTDs.
The haplotype GGGG, which consists of 4 SNPs (rs2236225, rs2236224, rs1256146, and rs6573559), is also associated with risk of NTDs (P value=0.0438, OR=0.7180, 95% CI=0.5214-0.9888).
A polymorphism, R653Q, in the trifunctional enzyme methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase/formyltetrahydrofolate synthetase is a maternal genetic risk factor for neural tube defects: report of the Birth Defects Research Group.
Molecular genetic analysis of the gene encoding the trifunctional enzyme MTHFD (methylenetetrahydrofolate-dehydrogenase, methenyltetrahydrofolate-cyclohydrolase, formyltetrahydrofolate synthetase) in patients with neural tube defects.
Molecular genetic analysis of the gene encoding the trifunctional enzyme MTHFD (methylenetetrahydrofolate-dehydrogenase, methenyltetrahydrofolate-cyclohydrolase, formyltetrahydrofolate synthetase) in patients with neural tube defects.
A polymorphism, R653Q, in the trifunctional enzyme methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase/formyltetrahydrofolate synthetase is a maternal genetic risk factor for neural tube defects: report of the Birth Defects Research Group.
After additional stratification of case and control groups according to sex and tumor type association of MTHFD1 G1958A with NHL was observed only in high-grade NHL subgroup (allele G OR=1.664, P=0.01) and in women subgroup (allele G OR=2.043, P=0.009).
MTHFD1 G1958A polymorphism was not associated with increased risk of this disease; the evaluation results of the MTHFR A1298C polymorphism in this neoplasm were contradictory.
The aim of this study was to investigate the association between MTHFR C677T, A1298C, MTHFD G1958A and plasminogen activator inhibitor type 1 (PAI-1) 4G/5G polymorphism among first trimester recurrent miscarriages.
Drinking water inorganic arsenic concentration was associated with increased risk of myelomeningocele for participants with 4 of the 14 studied single-nucleotide polymorphisms in genes involved in folate metabolism: the AA/AG genotype of rs2236225 (MTHFD1), the GG genotype of rs1051266 (SLC19A1), the TT genotype of rs7560488 (DNMT3A), and the GG genotype of rs3740393 (AS3MT) with adjusted odds ratio of 1.13, 1.31, 1.20, and 1.25 for rs2236225, rs1051266, rs7560488, and rs3740393, respectively.
For G1958A, a decreased cancer risk was found in acute lymphoblastic leukemia (ALL)/Asians (the dominant: OR = 0.74, 95% CI = 0.58-0.94, P = 0.01; allelic: OR = 0.80, 95% CI = 0.65-0.99, P = 0.04) and other cancers (recessive: OR = 0.80, 95% CI = 0.66-0.96, P = 0.02).