Reduced folate carrier polymorphisms and neural tube defect risk

Valerie B. O'Leary, Faith Pangilinan, Christopher Cox, Anne Parle-McDermott, Mary Conley, Anne M. Molloy, Peadar N. Kirke, James L. Mills, Lawrence C. Brody, John M. Scott

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


The reduced folate carrier (RFCI) is essential for folate transport into cells. Low folate is an important cause of neural tube defects (NTDs), and a single-nucleotide polymorphism (H27R) (80G→A) in the RFCI gene has been reported to be a NTD risk factor. We investigated H27R and a 61bp tandem repeat polymorphism as potential risk factors for NTDs, using a large homogeneous Irish population by case/control comparison, log-linear analysis, and transmission disequilibrium testing. No association was found between NTDs and H27R in mothers [p = 0.23, odds ratio (OR) 0.87, 95% confidence interval (CI) 0.69-1.09], fathers (p = 0.11, OR 0.83, 95% CI 0.66-1.04), or cases (p = 0.36, OR 0.9, 95% CI 0.72-1.12) when compared to controls or through log-linear modeling for dominant or recessive effects or with the transmission disequilibrium test for preferential allele transmission. Using log-linear models, a significant protective case effect was seen for the 61 bp polymorphism (p = 0.0039, OR 0.21, 95% CI 0.05-0.85). When analyzed by genotype, individuals homozygous for a single copy of the 61 bp sequence were underrepresented in cases as compared to controls, although these results did not reach statistical significance (p = 0.081, OR 0.5, 95% CI 0.23-1.09, goodness of fit p = 0.42). We compared the frequencies of H27R and the 61 bp polymorphism in African-Americans and American-Caucasians. The frequencies of H27R polymorphism differed significantly between the two populations (p = 0.0001). This large study does not confirm previous reports that H27R is a risk factor for NTDs. The previously unstudied 61 bp tandem repeat, however, has a possible protective NTD effect in our Irish population. This requires confirmation in other studies.

Original languageEnglish (US)
Pages (from-to)364-369
Number of pages6
JournalMolecular genetics and metabolism
Issue number4
StatePublished - Apr 2006
Externally publishedYes


  • 61 bp tandem repeat
  • Folate
  • H27R
  • Neural tube defect
  • Reduced folate carrier

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology


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