SOD2 as a potential modifier of X-linked adrenoleukodystrophy clinical phenotypes

Rebecca Deering Brose, Dimitri Avramopoulos, Kirby D. Smith

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


X-linked adrenoleukodystrophy (XALD), a neurological disorder caused by mutations in the peroxisomal membrane protein gene ABCD1, presents as a rapidly progressing, inflammatory cerebral demyelination (cerebral cases) or a slowly progressing, distal axonopathy (noncerebral cases). Specific ABCD1 defects do not explain this significant phenotypic variation. Patients have increased plasma and tissue very long chain fatty acid levels and increased cellular oxidative stress and oxidative damage. Superoxide dismutase 2 (SOD2), at candidate modifier locus 6q25.3, detoxifies superoxide radicals protecting against oxidative stress and damage. We tested an SOD2 variant C47T (Ala16Val) associated with reduced enzymatic activity as a potential modifier gene of cerebral demyelinating disease by comparing 117 cerebral XALD cases with 105 non-cerebral XALD cases. The hypoactive valine allele of the variant was associated with cerebral disease under a dominant model in the full data set (p = 0.04; ORT* = 1.90, 95% CI 1.01-3.56) and the non-childhood cerebral disease subset (p = 0.03; ORT* = 2.47, 95% CI 1.08-5.61). Three tag SNPs were genotyped to test for additional SNP or haplotype associations. A common haplotype, GTAC, which included the SOD2 valine allele, was associated with cerebral disease in the full data set (p = 0.03; OR = 1.75, 95% CI 1.11-2.75) and the non-childhood cerebral disease subset (p = 0.008; OR = 2.20, 95% CI 1.27-3.83). There was no association between childhood cerebral XALD and the C47T variant or the GTAC haplotype. Thus, reduced SOD2 activity may contribute to the development of cerebral demyelination in adolescent and adult XALD patients.

Original languageEnglish (US)
Pages (from-to)1440-1447
Number of pages8
JournalJournal of neurology
Issue number7
StatePublished - Jul 2012


  • Modifier gene
  • Neurogenetics
  • Oxidative stress
  • Superoxide dismutase 2 (SOD2)
  • X-linked adrenoleukodystrophy

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


Dive into the research topics of 'SOD2 as a potential modifier of X-linked adrenoleukodystrophy clinical phenotypes'. Together they form a unique fingerprint.

Cite this