Analysis of ALDH1A2, CYP26A1, CYP26B1, CRABP1, and CRABP2 in human neural tube defects suggests a possible association with alleles in ALDH1A2.
BACKGROUND
Vitamin A (retinol), in the form of retinoic acid (RA), is essential for normal development of the human embryo. Studies in the mouse and zebrafish have shown that retinol is metabolized in the developing spinal cord and must be maintained in a precise balance along the anteroposterior axis. Both excess and deficiency of RA can affect morphogenesis, including failures of neural tube closure.


METHODS
We chose to investigate 5 genes involved in the metabolism or synthesis of RA, ALDH1A2, CYP26A1, CYP26B1, CRABP1, and CRABP2, for their role in the development of human neural tube defects, such as spina bifida.


RESULTS
An association analysis using both allelic and genotypic single-locus tests revealed a significant association between the risk for spina bifida and 3 polymorphisms in the gene ALDH1A2; however, we found no evidence of a significant multilocus association.


CONCLUSIONS
These results may suggest that polymorphisms in ALDH1A2 may influence the risk for lumbosacral myelomeningocele in humans.
Deak
Kristen L
KL
Center for Human Genetics, Duke University Medical Center, Durham, North Carolina 27710, USA.
Dickerson
Margaret E
ME
Linney
Elwood
E
Enterline
David S
DS
George
Timothy M
TM
Melvin
Elizabeth C
EC
Graham
Felicia L
FL
Siegel
Deborah G
DG
Hammock
Preston
P
Mehltretter
Lorraine
L
Bassuk
Alexander G
AG
Kessler
John A
JA
Gilbert
John R
JR
Speer
Marcy C
MC
D000483:Alleles; D000818:Animals; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008591:Meningomyelocele / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D038081:Organogenesis / Q000235:genetics; D010088:Oxidoreductases / Q000235:genetics*; D011110:Polymorphism, Genetic; D040641:Quantitative Trait Loci; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D014801:Vitamin A / Q000235:genetics / Q000378:metabolism
D018168:Receptors, Retinoic Acid; C082928:retinoic acid binding protein II, cellular; D014801:Vitamin A; D010088:Oxidoreductases