title: 5,10 Methylenetetrahydrofolate reductase genetic polymorphism as a risk factor for neural tube defects.
abstract: Persons with a thermolabile form of the enzyme 5,10 methylenetetrahydrofolate reductase (MTHFR) have reduced enzyme activity and increased plasma homocysteine which can be lowered by supplemental folic acid. Thermolability of the enzyme has recently been shown to be caused by a common mutation (677C-->T) in the MTHFR gene. We studied 41 fibroblast cultures from NTD-affected fetuses and compared their genotypes with those of 109 blood specimens from individuals in the general population. 677C-->T homozygosity was associated with a 7.2 fold increased risk for NTDs (95% confidence interval: 1.8-30.3; p value: 0.001). These preliminary data suggest that the 677C-->T polymorphism of the MTHFR gene is a risk factor for spina bifida and anencephaly that may provide a partial biologic explanation for why folic acid prevents these types of NTD.
authors.affiliation: Division of Environmental Health Laboratory Sciences, Centers for Disease Control and Prevention, Atlanta, Georgia 30341-3724, USA.
authors.forename: C Y
authors.initials: CY
authors.lastname: Ou
authors.forename: R E
authors.initials: RE
authors.lastname: Stevenson
authors.forename: V K
authors.initials: VK
authors.lastname: Brown
authors.forename: C E
authors.initials: CE
authors.lastname: Schwartz
authors.forename: W P
authors.initials: WP
authors.lastname: Allen
authors.forename: M J
authors.initials: MJ
authors.lastname: Khoury
authors.forename: R
authors.initials: R
authors.lastname: Rozen
authors.forename: G P
authors.initials: GP
authors.lastname: Oakley
authors.forename: M J
authors.initials: MJ
authors.lastname: Adams
mesh_terms: D045103:5,10-Methylenetetrahydrofolate Reductase (FADH2); D000328:Adult; D001741:Black or African American; D000483:Alleles; D000757:Anencephaly / Q000201:enzymology / Q000235:genetics; D004795:Enzyme Stability; D005260:Female; D005333:Fetus / Q000002:abnormalities / Q000166:cytology / Q000473:pathology; D006720:Homozygote; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008969:Molecular Sequence Data; D009436:Neural Tube Defects / Q000201:enzymology* / Q000235:genetics*; D010088:Oxidoreductases / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D016135:Spinal Dysraphism / Q000201:enzymology / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: D010088:Oxidoreductases; D045103:5,10-Methylenetetrahydrofolate Reductase (FADH2); D042965:Methylenetetrahydrofolate Reductase (NADPH2)