Reduced folate carrier polymorphisms and neural tube defect risk.
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.
O'leary
Valerie B
VB
Department of Biochemistry, Trinity College Dublin, Ireland. olearyv@tcd.ie
Pangilinan
Faith
F
Cox
Christopher
C
Parle-McDermott
Anne
A
Conley
Mary
M
Molloy
Anne M
AM
Kirke
Peadar N
PN
Mills
James L
JL
Brody
Lawrence C
LC
Scott
John M
JM
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
D026901:Membrane Transport Proteins; D058978:Reduced Folate Carrier Protein; C548699:SLC19A1 protein, human