Analysis of the human folate receptor (beta) gene for an association with neural tube defects

The folate receptor (beta) (FR(beta)) gene encodes a receptor that binds and transports 5-methyltetrahydrofolate. FR(beta) polymorphisms may potentially alter folate delivery and are likely candidates for an association with neural tube defect (NTD) risk. To look for association between FR(beta) 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 NTDaffected child. Five potential single nucleotide polymorphisms (SNPs) were examined. These were located within the coding, intronic and 3ʹ-untranslated regions of the FR(beta) gene. Four of these SNPs were not found to be variable within our Irish cohort. SNP rs651646 (A (longrightarrow) T), located upstream of exon 2 within an intronic region, is polymorphic and is thus a marker for an FR(beta) 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 X^2 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 FR(beta) gene is polymorphic but is not associated with neural tube defects within the Irish population.