Associations between multiple system atrophy and polymorphisms of SLC1A4, SQSTM1, and EIF4EBP1 genes
Associations between multiple system atrophy and polymorphisms of SLC1A4, SQSTM1, and EIF4EBP1 genes
复制标题
DOI：
10.1002/mds.22046
复制
发表时间：
2008-06-15
影响因子：
8.6
通讯作者：
Sasaki, Hidenao
中科院分区：
文献类型：
--
作者：
Soma, Hiroyuki;Yabe, Ichiro;Sasaki, Hidenao
多系统萎缩（MSA）是一种成人发病的散发性神经退行性疾病。虽然MSA的病因仍然不清楚，但最近的研究表明，氧化应激与MSA的发病机制有关。本研究的目的是在病例对照研究中评估参与氧化应激和MSA的候选基因之间的遗传关联。我们检查了119名日本MSA患者和123名对照，并对以下8个基因的单核苷酸多态性（SNP）进行了基因分型：CCAAT/增强子结合蛋白同源蛋白，转录激活因子3，CCAAT/增强子结合蛋白-P，隔离体1（SQSTM 1），半胱氨酰-tRNA合成酶，溶质载体家族1A 4（SLC 1A 4），转录激活因子4，和真核翻译起始因子4 E结合蛋白1（EIF 4 EBP 1）。SLC1A4 SNP +28833（V398 I，rs759458，基因型：Pc = 0.0186，等位基因：Pc = 0.0303，Pc：P值与Bonferroni校正），SLC 1A 4的两种主要单倍型“T-C-C-G”和“T-C-T-A”SQSTM 1的“C-T”和“A-T”单倍型（Pc = 0.0136和0.0369）以及EIF 4 EBP 1的最常见单倍型“C-T-G-C”（Pc = 0.0480）显示了显著的关联。这项研究揭示了SLC 1A 4，SQSTM 1和EIF 4 EBP 1与MSA的遗传关联。这些结果可能倾向于遗传支持的假设，氧化应激与MSA的发病机制。(C)2008年，《社会运动》创刊。
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-P, 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 tend genetic support to the hypothesis that oxidative stress is associated with the pathogenesis of MSA. (C) 2008 Movement Disorder Society.