Association of folate receptor (FOLR1, FOLR2, FOLR3) and reduced folate carrier (SLC19A1) genes with meningomyelocele.
BACKGROUND
Meningomyelocele (MM) results from lack of closure of the neural tube during embryologic development. Periconceptional folic acid supplementation is a modifier of MM risk in humans, leading toan interest in the folate transport genes as potential candidates for association to MM.


METHODS
This study used the SNPlex Genotyping (ABI, Foster City, CA) platform to genotype 20 single polymorphic variants across the folate receptor genes (FOLR1, FOLR2, FOLR3) and the folate carrier gene (SLC19A1) to assess their association to MM. The study population included 329 trio and 281 duo families. Only cases with MM were included. Genetic association was assessed using the transmission disequilibrium test in PLINK.


RESULTS
A variant in the FOLR2 gene (rs13908), three linked variants in the FOLR3 gene (rs7925545, rs7926875, rs7926987), and two variants in the SLC19A1 gene (rs1888530 and rs3788200) were statistically significant for association to MM in our population.


CONCLUSIONS
This study involved the analyses of selected single nucleotide polymorphisms across the folate receptor genes and the folate carrier gene in a large population sample. It provided evidence that the rare alleles of specific single nucleotide polymorphisms within these genes appear to be statistically significant for association to MM in the patient population that was tested.
O'Byrne
Michelle R
MR
Department of Pediatrics, The University of Texas Medical School at Houston, Houston, Texas 77030, USA.
Au
Kit Sing
KS
Morrison
Alanna C
AC
Lin
Jone-Ing
JI
Fletcher
Jack M
JM
Ostermaier
Kathryn K
KK
Tyerman
Gayle H
GH
Doebel
Sabine
S
Northrup
Hope
H
D000293:Adolescent; D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D058975:Folate Receptor 1 / Q000235:genetics*; D058976:Folate Receptor 2 / Q000235:genetics*; D056726:Genetic Association Studies; D008040:Genetic Linkage; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D008591:Meningomyelocele / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D058978:Reduced Folate Carrier Protein / Q000235:genetics*; D044465:White People / Q000235:genetics; D055815:Young Adult
D002352:Carrier Proteins; C548697:FOLR3 protein, human; D058975:Folate Receptor 1; D058976:Folate Receptor 2; D058978:Reduced Folate Carrier Protein; C548699:SLC19A1 protein, human