An altered antioxidant balance occurs in Down syndrome fetal organs: implications for the "gene dosage effect" hypothesis

J Neural Transm Suppl. 2003;(67):67-83. doi: 10.1007/978-3-7091-6721-2_6.


Down syndrome (DS) is the congenital birth defect responsible for the greatest number of individuals with mental retardation. It arises due to trisomy of human chromosome 21 (HSA21) or part thereof. To date there have been limited studies of HSA21 gene expression in trisomy 21 conceptuses. In this study we investigate the expression of the HSA21 antioxidant gene, Cu/Zn-superoxide dismutase-1 (SOD1) in various organs of control and DS aborted conceptuses. We show that SOD1 mRNA levels are elevated in DS brain, lung, heart and thymus. DS livers show decreased SOD1 mRNA expression compared with controls. Since non-HSA21 antioxidant genes are reported to be concomitantly upregulated in certain DS tissues, we examined the expression of glutathione peroxidase-1 (GPX1) in control and DS fetal organs. Interestingly, GPX1 expression was unchanged in the majority of DS organs and decreased in DS livers. We examined the SOD1 to GPX1 mRNA ratio in individual organs, as both enzymes form part of the body's defense against oxidative stress, and because a disproportionate increase of SOD1 to GPX1 results in noxious hydroxyl radical damage. All organs investigated show an approximately 2-fold increase in the SOD1 to GPX1 mRNA ratio. We propose that it is the altered antioxidant ratio that contributes to certain aspects of the DS phenotype.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / metabolism*
  • Down Syndrome / enzymology*
  • Down Syndrome / genetics*
  • Fetus / enzymology*
  • Fetus / metabolism
  • Gene Dosage*
  • Gene Expression Regulation, Enzymologic / physiology
  • Glutathione Peroxidase / biosynthesis
  • Glutathione Peroxidase / genetics
  • Humans
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Statistics, Nonparametric
  • Superoxide Dismutase / biosynthesis
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase-1


  • Antioxidants
  • RNA, Messenger
  • SOD1 protein, human
  • glutathione peroxidase GPX1
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Superoxide Dismutase-1