SOD2 as a potential modifier of X-linked adrenoleukodystrophy clinical phenotypes
| Autor: | Kirby D. Smith, Dimitri Avramopoulos, Rebecca Deering Brose |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Genotype Very long chain fatty acid SOD2 Single-nucleotide polymorphism Biology medicine.disease_cause Polymorphism Single Nucleotide Young Adult chemistry.chemical_compound Gene Frequency Internal medicine Demyelinating disease medicine Humans Genetic Predisposition to Disease Age of Onset Allele Adrenoleukodystrophy Child Genetics Chi-Square Distribution Superoxide Dismutase Haplotype medicine.disease Phenotype Endocrinology Neurology chemistry Case-Control Studies Child Preschool Neurology (clinical) Oxidative stress |
| Zdroj: | Journal of Neurology. 259:1440-1447 |
| ISSN: | 1432-1459 0340-5354 |
| Popis: | 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 (non-cerebral 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. |
| Databáze: | OpenAIRE |
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