Updated investigations of the role of methylenetetrahydrofolate reductase in human neural tube defects.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Rampersaud, E; Melvin, EC; Siegel, D; Mehltretter, L; Dickerson, ME; George, TM; Enterline, D; Nye, JS; Speer, MC; NTD Collaborative Group,

Published Date

  • March 2003

Published In

Volume / Issue

  • 63 / 3

Start / End Page

  • 210 - 214

PubMed ID

  • 12694231

International Standard Serial Number (ISSN)

  • 0009-9163

Digital Object Identifier (DOI)

  • 10.1034/j.1399-0004.2003.00043.x


  • eng

Conference Location

  • Denmark