title: Reduced folate carrier polymorphisms and neural tube defect risk.
abstract: 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 61 bp 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.
authors.affiliation: Department of Biochemistry, Trinity College Dublin, Ireland. olearyv@tcd.ie
authors.forename: Valerie B
authors.initials: VB
authors.lastname: O'leary
authors.forename: Faith
authors.initials: F
authors.lastname: Pangilinan
authors.forename: Christopher
authors.initials: C
authors.lastname: Cox
authors.forename: Anne
authors.initials: A
authors.lastname: Parle-McDermott
authors.forename: Mary
authors.initials: M
authors.lastname: Conley
authors.forename: Anne M
authors.initials: AM
authors.lastname: Molloy
authors.forename: Peadar N
authors.initials: PN
authors.lastname: Kirke
authors.forename: James L
authors.initials: JL
authors.lastname: Mills
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Brody
authors.forename: John M
authors.initials: JM
authors.lastname: Scott
mesh_terms: D001741:Black or African American; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D026901:Membrane Transport Proteins / Q000235:genetics*; D009436:Neural Tube Defects / Q000208:ethnology / Q000235:genetics*; D011110:Polymorphism, Genetic; D011247:Pregnancy; D058978:Reduced Folate Carrier Protein; D012307:Risk Factors; D020080:Tandem Repeat Sequences; D044465:White People
chemical_list: D026901:Membrane Transport Proteins; D058978:Reduced Folate Carrier Protein; C548699:SLC19A1 protein, human