title: Association of copper-zinc superoxide dismutase (SOD1) and manganese superoxide dismutase (SOD2) genes with nonsyndromic myelomeningocele.
abstract: BACKGROUND
  A common and severe neural tube defect (NTD) phenotype, myelomeningocele (MM), results from the defective closure of the caudal end of the neural tube with herniation of the spinal cord and meninges through the vertebral column. The exact mechanisms for NTDs are unknown, but excessive oxidative stress, particularly in association with maternal diabetes, has been postulated as a mechanism for MM.
  
  
  METHODS
  The SNPlex Genotyping (ABI, Foster City, CA) platform was used to investigate single nucleotide polymorphisms (SNPs) across the superoxide dismutase (SOD) 1 and 2 genes to assess their association with MM risk. The study population included 329 trio (affected child and both parents) and 281 duo (affected child and one parent) families. Only cases with documented MM were studied. Seventeen SNPs across the SOD1 and SOD2 genes met the quality-control criteria to be considered for statistical analysis. Genetic association was assessed using the family-based transmission disequilibrium test in PLINK (a genome association analysis toolset).
  
  
  RESULTS
  Four SNPs in the SOD1 gene (rs 202446, rs202447, rs4816405, and rs2070424) and one SNP in the SOD2 gene ( rs5746105) [corrected] appeared to be associated with MM risk in our population. After adjusting for multiple testing, these SNPs remained significant.
  
  
  CONCLUSIONS
  This study provides the first genetic evidence to support association of myelomeningocele with superoxide scavenging. The rare alleles of the five specific SNPs within SOD1 and SOD2 appear to confer a protective effect on the susceptibility for MM risk in the MM population tested. Further evaluation of the roles of superoxide scavenging and neural tube development is warranted.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, The University of Texas Medical School at Houston, Houston, TX 77030, USA.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Kase
authors.forename: Hope
authors.initials: H
authors.lastname: Northrup
authors.forename: Alanna C
authors.initials: AC
authors.lastname: Morrison
authors.forename: Christina M
authors.initials: CM
authors.lastname: Davidson
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Goiffon
authors.forename: Jack M
authors.initials: JM
authors.lastname: Fletcher
authors.forename: Kathryn K
authors.initials: KK
authors.lastname: Ostermaier
authors.forename: Gayle H
authors.initials: GH
authors.lastname: Tyerman
authors.forename: Kit Sing
authors.initials: KS
authors.lastname: Au
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005190:Family; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D008297:Male; D008591:Meningomyelocele / Q000453:epidemiology / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D055815:Young Adult; D000099156:Superoxide Dismutase 2
chemical_list: D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2; C000606290:SOD1 protein, human