Analysis of the MTHFD1 promoter and risk of neural tube defects

摘要: Genetic variants in MTHFD1 (5,10-methylenetetrahydrofolate dehydrogenase/5,10-methenyltetrahydrofolate cyclohydrolase/ 10-formyltetrahydrofolate synthetase), an important folate metabolic enzyme, are associated with a number of common diseases, including neural tube defects (NTDs). This study investigates the promoter human gene bid to understand how this is controlled and regulated. Following combination silico molecular approaches, we report that expression by TATA-less, Initiator-less transcription initiated at multiple start sites over 126 bp region. We confirmed presence three database polymorphisms (dbSNP) direct sequencing upstream region (rs1076991 C > T, rs8010584 G > A, rs4243628 G > T), fourth (dbSNP rs746488 A > T) not found be polymorphic our population no novel identified. demonstrate SNP rs1076991 C > T within window transcriptional initiation exerts significant effect on activity vitro. investigated as potential risk factor for NTDs large homogenous Irish determined it independent factor, but, does increase both case (χ 2 = 11.06, P = 0.001) maternal 2 = 6.68, P = 0.01) when allele frequencies were analysed previously identified disease-associated p.R653Q (c.1958 G > A; dbSNP rs2236225) polymorphism. These results provide first insight into regulated further emphasise its importance during embryonic development.