Association of retinoic acid receptor genes with meningomyelocele.
BACKGROUND
Neural tube defects (NTDs) occur in as many as 0.5-2 per 1000 live births in the United States. One of the most common and severe neural tube defects is meningomyelocele (MM) resulting from failed closure of the caudal end of the neural tube. MM has been induced by retinoic acid teratogenicity in rodent models. We hypothesized that genetic variants influencing retinoic acid (RA) induction via retinoic acid receptors (RARs) may be associated with risk for MM.


METHODS
We analyzed 47 single nucleotide polymorphisms (SNPs) that span across the three retinoic acid receptor genes using the SNPlex genotyping platform. Our cohort consisted of 610 MM families.


RESULTS
One variant in the RARA gene (rs12051734), three variants in the RARB gene (rs6799734, rs12630816, rs17016462), and a single variant in the RARG gene (rs3741434) were found to be statistically significant at p < 0.05.


CONCLUSIONS
RAR genes were associated with risk for MM. For all associated SNPs, the rare allele conferred a protective effect for MM susceptibility.
Department of Pediatrics, University of Texas Medical School at Houston, TX 77030, USA.
Phong X
PX
Tran
Kit Sing
KS
Au
Alanna C
AC
Morrison
Jack M
JM
Fletcher
Kathryn K
KK
Ostermaier
Gayle H
GH
Tyerman
Hope
H
Northrup
D000483:Alleles; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D008297:Male; D008591:Meningomyelocele / Q000208:ethnology / Q000235:genetics*; D009436:Neural Tube Defects / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D000072482:Retinoic Acid Receptor alpha; D044465:White People / Q000235:genetics; D000097768:Retinoic Acid Receptor gamma
D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D000097768:Retinoic Acid Receptor gamma; C000607071:RARA protein, human; C082925:retinoic acid receptor beta
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