Associations between multiple system atrophy and polymorphisms of SLC1A4, SQSTM1, and EIF4EBP1 genes

Multiple system atrophy (MSA) is an adult-onset sporadic neurodegenerative disease. Although the etiology of MSA remains obscure, recent studies suggest that oxidative stress is associated with the pathogenesis of MSA. The aim of this study was to evaluate genetic associations between the candidate genes involved in oxidative stress and MSA in a case-control study. We examined 119 Japanese patients with MSA and 123 controls, and genotyped single-nucleotide polymorphisms (SNPs) of the following eight genes: CCAAT/enhancer-binding protein homologous protein, activating transcription factor 3, CCAAT/enhancer-binding protein-beta, sequestosome 1 (SQSTM1), cysteinyl-tRNA synthetase, solute carrier family 1A4 (SLC1A4), activating transcription factor 4, and eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1). SLC1A4 SNP +28833 (V398I, rs759458, genotype: Pc = 0.0186, allele: Pc = 0.0303, Pc: P-value with Bonferroni correction), two major haplotypes of SLC1A4 "T-C-C-G" and "T-C-T-A" (Pc = 0.0261 and 0.000768), two-SNP haplotypes of SQSTM1 "C-T" and "A-T" (Pc = 0.0136 and 0.0369), and the most common haplotype of EIF4EBP1 "C-T-G-C" (Pc = 0.0480) showed significant associations. This study revealed genetic associations of SLC1A4, SQSTM1, and EIF4EBP1 with MSA. These results may lend genetic support to the hypothesis that oxidative stress is associated with the pathogenesis of MSA.