Department of Neurology & Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Curr Alzheimer Res. 2011 Nov;8(7):765-70. doi: 10.2174/156720511797633232.
Apolipoprotein E (APOE) ε4 allele and sigma-1 receptor (SIGMAR1) c.5C (Q2P) polymorphisms have been acknowledged as risk factors for developing Alzheimer's disease (AD). However, whether these polymorphisms influence the disease process is unclear. Therefore, two cohorts with a clinical diagnosis of AD were recruited, a postmortem confirmed Australian cohort (82 cases) from the Australian Brain Bank Network, and a Chinese cohort with detailed clinical assessments recruited through an epidemiology study in Shanghai and through the neurology department outpatients clinic of Shanghai Ruijin Hospital (330 cases). SIGMAR1 Q2P and APOE genotyping was performed on all cases. Dementia severity in the Chinese cohort was assessed using MMSE scores, and the stages of senile plaques and neurofibrillary tangles (NFT) assessed in the Australian cohort. Associations between SIGMAR1 Q2P and APOE genotypes and disease severity were assessed using SPSS. Results confirmed that APOE 4 allele associated with increased NFT stages and cognitive decline, with carriers with one APOE ε2 or ε3 allele often having better clinical outcomes compared to carriers with none or two ε2 or ε3 alleles respectively. SIGMAR1 c.5C polymorphism alone did not associate with MMSE score variability in Chinese or with pathological stages in Caucasians. However, the association studies revealed a significant genetic interaction between the APOE ε4 allele and SIGMAR1 2P carriers in both populations, i.e., in APOE non ε4 allele carriers, SIGMAR1 2P variant had increased cognitive dysfunction and more advanced stages of NFT. Our data demonstrate that SIGMAR1 and APOE interact to influence AD severity across ethnic populations.
载脂蛋白 E (APOE) ε4 等位基因和 sigma-1 受体 (SIGMAR1) c.5C (Q2P) 多态性已被认为是阿尔茨海默病 (AD) 发病的危险因素。然而，这些多态性是否影响疾病进程尚不清楚。因此，我们招募了两个具有 AD 临床诊断的队列，一个是来自澳大利亚脑库网络的死后确诊的澳大利亚队列（82 例），另一个是在中国上海进行的流行病学研究和通过上海瑞金医院神经内科门诊招募的具有详细临床评估的中国队列（330 例）。对所有病例进行了 SIGMAR1 Q2P 和 APOE 基因分型。中国队列的痴呆严重程度使用 MMSE 评分评估，澳大利亚队列的老年斑和神经原纤维缠结 (NFT) 分期评估。使用 SPSS 评估 SIGMAR1 Q2P 和 APOE 基因型与疾病严重程度之间的关系。结果证实，APOE 4 等位基因与 NFT 分期和认知能力下降增加相关，与携带一个 APOE ε2 或 ε3 等位基因的携带者相比，分别与不携带或携带两个 APOE ε2 或 ε3 等位基因的携带者相比，具有更好的临床结局。SIGMAR1 c.5C 多态性单独与中国人的 MMSE 评分变异性或白种人的病理分期均无关。然而，关联研究揭示了 APOE ε4 等位基因和 SIGMAR1 2P 携带者在两个人群中的显著遗传相互作用，即在 APOE 非 ε4 等位基因携带者中，SIGMAR1 2P 变体增加了认知功能障碍和更高级别的 NFT 分期。我们的数据表明，SIGMAR1 和 APOE 相互作用，影响跨种族人群的 AD 严重程度。
