title: Analysis of the human folate receptor beta gene for an association with neural tube defects.
abstract: The folate receptor beta (FRbeta) gene encodes a receptor that binds and transports 5-methyltetrahydrofolate. FRbeta polymorphisms may potentially alter folate delivery and are likely candidates for an association with neural tube defect (NTD) risk. To look for association between FRbeta 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 FRbeta 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 FRbeta 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 chi(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 FRbeta gene is polymorphic but is not associated with neural tube defects within the Irish population.
authors.affiliation: Department of Biochemistry, Trinity College Dublin, Dublin, Ireland. olearyv@tcd.ie
authors.forename: Valerie B
authors.initials: VB
authors.lastname: O'Leary
authors.forename: James L
authors.initials: JL
authors.lastname: Mills
authors.forename: Peadar N
authors.initials: PN
authors.lastname: Kirke
authors.forename: Anne
authors.initials: A
authors.lastname: Parle-McDermott
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Swanson
authors.forename: Andrea
authors.initials: A
authors.lastname: Weiler
authors.forename: Faith
authors.initials: F
authors.lastname: Pangilinan
authors.forename: Mary
authors.initials: M
authors.lastname: Conley
authors.forename: Anne M
authors.initials: AM
authors.lastname: Molloy
authors.forename: Miriam
authors.initials: M
authors.lastname: Lynch
authors.forename: Christopher
authors.initials: C
authors.lastname: Cox
authors.forename: John M
authors.initials: JM
authors.lastname: Scott
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Brody
mesh_terms: D020413:3' Untranslated Regions; D001741:Black or African American; D044383:Black People / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D005260:Female; D058973:Folate Receptors, GPI-Anchored; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns; D007494:Ireland; D008297:Male; D009436:Neural Tube Defects / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011956:Receptors, Cell Surface; D044465:White People / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface