Joanna Aben, Children's Rehabilitation Service, Birmingham, Alabama; Arthur Aylsworth, Cynthia Powell, University of North Carolina, Chapel Hill, North Carolina; Timothy Brei, Connie Buran, Indiana University School of Medicine, Indiana- polis, Indiana; Joann Bodurtha, Kathleen Sawin, Medical College of Virginia, Richmond, Virginia; Mark S. Dias, Children's Hospital of Buffalo, Buffalo, NY; Bermans Iskandar, Bonnie Ohm, University of Wisconsin Hospitals, Madison, Wisconsin; Nicole Lasarsky, Carolinas Medical Center, Charlotte, NC; David McLone, Joy Ito, Children's Memorial Hospital, Chicago, Illinois; W. Jerry Oakes, University of Alabama, Birmingham, Alabama; Marion Walker, Paula Peterson, University of Utah, Salt Lake City, Utah.
Updated investigations of the role of methylenetetrahydrofolate reductase in human neural tube defects
Version of Record online: 12 APR 2003
Volume 63, Issue 3, pages 210–214, March 2003
How to Cite
Rampersaud, E., Melvin, E., Siegel, D., Mehltretter, L., Dickerson, M., George, T., Enterline, D., Nye, J., Speer, M. and the NTD Collaborative Group (2003), Updated investigations of the role of methylenetetrahydrofolate reductase in human neural tube defects. Clinical Genetics, 63: 210–214. doi: 10.1034/j.1399-0004.2003.00043.x
- Issue online: 12 APR 2003
- Version of Record online: 12 APR 2003
- Received 23 August 2002, revised and accepted for publication 13 November 2002
- cystathionine beta-synthase;
- gene–environment interactions;
- methylenetetrahydrofolate reductase;
- neural tube defects
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 β-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.