AbstractBACKGROUNDNeural 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.METHODSWe 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.RESULTSOne 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.CONCLUSIONRAR genes were associated with risk for MM. For all associated SNPs, the rare allele conferred a protective effect for MM susceptibility. Birth Defects Research (Part A), 2011. © 2010 Wiley‐Liss, Inc.