Gheens Center on Aging, Department of Biochemistry and Molecular Biology, School of Medicine, University of Louisville, Louisville, KY 40202, USA.
Neurobiol Aging. 2010 Jan;31(1):34-45. doi: 10.1016/j.neurobiolaging.2008.03.007. Epub 2008 Apr 17.
Brain-specific glutathione S-transferase Mu 3 (GSTM3) colocalizes with amyloid-beta plaques in Alzheimer's disease (AD). A functional polymorphism rs7483 in GSTM3 may contribute to the decrease in GSTM3 expression in AD. The association of the rs7483 SNP with late-onset AD and mild cognitive impairment (MCI) was evaluated and the impact of a SNP background on gene expression was analyzed in blood mononuclear cells (BMC). The allelic association of the GSTM3 allele with AD was significant in women and in APOEvarepsilon4-negative stratum. A significant association was also found in both MCI and AD subjects with AD family history. GSTM3 transcript levels in BMC were lower in AD than in normal elderly controls, and the presence of the risk allele was associated with further mRNA reduction. Diminished GSTM3 mRNA levels correlated with decreased minichromosome maintenance deficient 3 (MCM3) mRNA levels in a diagnostic and SNP-dependent fashion. Reduced antioxidant defense and genome maintenance associated with the GSTM3 polymorphism suggest a common hub of regulatory networks which, when impaired, may lead to AD.
脑特异性谷胱甘肽 S-转移酶 Mu3 (GSTM3)与阿尔茨海默病 (AD) 中的淀粉样β斑块共存。GSTM3 中的功能性多态性 rs7483 可能导致 AD 中 GSTM3 表达的减少。评估了 rs7483 SNP 与迟发性 AD 和轻度认知障碍 (MCI) 的关联，并在血液单核细胞 (BMC) 中分析了 SNP 背景对基因表达的影响。GSTM3 等位基因与 AD 的等位基因关联在女性和 APOE varepsilon4 阴性分层中具有显著性。在具有 AD 家族史的 MCI 和 AD 受试者中也发现了显著关联。与正常老年对照组相比，AD 患者 BMC 中的 GSTM3 转录本水平较低，风险等位基因的存在与进一步的 mRNA 减少相关。以诊断和 SNP 依赖的方式，降低的 GSTM3 mRNA 水平与降低的微小染色体维持缺陷 3 (MCM3) mRNA 水平相关。与 GSTM3 多态性相关的抗氧化防御和基因组维持能力降低表明存在一个共同的调控网络枢纽，当该枢纽受损时，可能导致 AD。
