A polymorphism in SOD2 is associated with development of Alzheimer’s disease

Abstract

Genes involved in cellular mechanisms to repair oxidative damage are strong candidates as etiologic factors for Alzheimer’s disease (AD). One important enzyme involved in this mechanism is superoxide dismutase 2 (SOD2). The gene for this enzyme lies within a single haplotype block at 6q25.3, a region showing evidence for linkage to AD in a genome scan. We genotyped four single nucleotide polymorphisms (SNPs) in SOD2 in families of the National Institute of Mental Health‐AD Genetics Initiative (ADGI): rs2758346 in the 5′ untranslated region (UTR), rs4880 in exon 2, rs2855116 in intron 3 and rs5746136 in the 3′UTR. Under a dominant model, family‐based association tests showed significant evidence for association of AD with the first three loci in a candidate gene set of families with individuals having age of onset of at least 50 years and two affected and one unaffected sibling, and in a late‐onset subset of families (families with all affected individuals having age of onset of at least 65 years) from the full ADGI sample. The alleles transmitted more frequently to cases than expected under the null hypothesis were T, C, G, and G. Global tests of the transmission of haplotypes indicate that the first two loci have the most consistent association with risk of AD. Because of the high linkage disequilibrium in this small (14 kb) gene, and the presence of 100 SNPs in this gene, 26 of which may have functional significance, additional genotyping and sequencing are needed to identify the functionally relevant SNP. We discuss the importance of our findings and the relevance of SOD2 to AD risk.

Dual Role of Superoxide Dismutase 2 Induced in Activated Microglia

“…Polymorphisms of SOD2 have been reported to be associated with the development of neurodegenerative diseases, such as Alzheimer disease (51) and Parkinson disease (52,53), as well as psychiatric disorders, such as schizophrenia (54), depression (55), and bipolar disorder (56). Notably, neuroinflammation is closely linked to the onset and/or development of these CNS diseases (1)(2)(3)(4)(5).…”

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

“…Other variants in SOD2 or an interplay of other genetic variants and environmental or stochastic factors may modify the development of cerebral disease and phenotypic heterogeneity in XALD. In the SOD2 gene region there are over 100 SNPs including at least 18 with possible functional significance and eight coding SNPs that result in nonsynomymous changes (http://ensembl.org) [31]. Some of these polymorphisms may account for the 56-fold variation in SOD2 enzymatic activity observed in healthy individuals and may contribute to the development of cerebral demyelination in XALD patients [21].…”

Differential Proteomics Analysis of Specific Carbonylated Proteins in the Temporal Cortex of Aged Rats: The Deterioration of Antioxidant System

“…Prdx1 plays its crucial role in the conversion of hydrogen peroxide to water to defend against oxidative damage [34]. Previous studies indicated that the dysfunctions of SOD1, SOD2, and Prdx1 implicated in the elevated oxidative stress in the brains of normal aging and patients with neurodegenerative diseases [21,23,35,36]. PPIA catalyzes the isomerization of proline imidic peptide bonds and accelerates the folding of proteins [37].…”