title: Updated investigations of the role of methylenetetrahydrofolate reductase in human neural tube defects.
abstract: Folate supplementation appears to reduce the risk for neural tube defects (NTDs). Methylenetetrahydrofolate reductase (MTHFR) is a candidate gene in the folate metabolism pathway that has been extensively studied in different human populations. We examined the risk associated with having the thermolabile variant (TT) of MTHFR in a study of 175 American Caucasians with NTDs and their families. We found a significant association in patients compared with 195 unrelated controls [odds ratio (OR) = 2.13, 95% confidence interval (95% CI) = 1.11-4.09)], but not in mothers (OR = 1.29, 95% CI = 0.622-2.67) or in fathers (OR = 1.45, 95% CI = 0.681-3.09). We found no evidence for unequal transmission from parents to an affected child (p > 0.10). We failed to find a previously reported association for a combined haplotype for MTHFR and cystathionine beta-synthase, except in subjects with NTDs compared with 559 pooled controls (OR = 2.87, 95% CI = 1.03-8.03). We found no evidence for an association for a novel CA-repeat polymorphism identified in a gene closely linked to MTHFR (p > 0.10). Our studies continue to suggest that additional candidate genes other than MTHFR may be responsible for an increased risk to NTD in some American Caucasian families.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: E
authors.initials: E
authors.lastname: Rampersaud
authors.forename: E C
authors.initials: EC
authors.lastname: Melvin
authors.forename: D
authors.initials: D
authors.lastname: Siegel
authors.forename: L
authors.initials: L
authors.lastname: Mehltretter
authors.forename: M E
authors.initials: ME
authors.lastname: Dickerson
authors.forename: T M
authors.initials: TM
authors.lastname: George
authors.forename: D
authors.initials: D
authors.lastname: Enterline
authors.forename: J S
authors.initials: JS
authors.lastname: Nye
authors.forename: M C
authors.initials: MC
authors.lastname: Speer
mesh_terms: D003541:Cystathionine beta-Synthase / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D009154:Mutation / Q000235:genetics; D009436:Neural Tube Defects / Q000235:genetics*; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000172:deficiency* / Q000235:genetics*; D014481:United States
chemical_list: D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D003541:Cystathionine beta-Synthase