Analysis of the human folate receptor β gene for an association with neural tube defects

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

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


The folate receptor β (FRβ) gene encodes a receptor that binds and transports 5-methyltetrahydrofolate. FRβ polymorphisms may potentially alter folate delivery and are likely candidates for an association with neural tube defect (NTD) risk. To look for association between FRβ polymorphisms we studied NTD-affected children and their parents (254 triads) recruited throughout Ireland and a control population of 296 pregnant women who did not give birth to an NTD-affected child. Five potential single nucleotide polymorphisms (SNPs) were examined. These were located within the coding, intronic and 3-untranslated regions of the FRβ gene. Four of these SNPs were not found to be variable within our Irish cohort. SNP rs651646 (A→T), located upstream of exon 2 within an intronic region, is polymorphic and is thus a marker for an FRβ NTD association study. The frequency of the SNP rs651646 "A" allele was not significantly different in cases (odds ratio [OR] 1.07, 95% CI. 0.84-1.36; P=0.60), their mothers (odds ratio [OR] 1.09, 95% CI. 0.86-1.38; P=0.51) or fathers (odds ratio [OR] 1.09, 95% CI. 0.86-1.38; P=0.50) when compared to controls. Comparisons of allele transmission from 255 informative heterozygous parents of NTD cases showed no preferential transmission of either the A or T alleles (A: 50.2%, n=128; T: 49.8%, n=127; P=1.00, McNemar χ2 0.0). We also measured allele frequencies in a sample of American-Caucasians and African-Americans. Highly significant allele frequency differences were observed between populations. In conclusion, SNP rs651646 within the FRβ gene is polymorphic but is not associated with neural tube defects within the Irish population.

Original languageEnglish (US)
Pages (from-to)129-133
Number of pages5
JournalMolecular genetics and metabolism
Issue number2
StatePublished - Jun 1 2003
Externally publishedYes


  • Folate
  • Folate receptor
  • Neural tube defects
  • Polymorphism
  • Spina bifida

ASJC Scopus subject areas

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


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