University of Szeged, Department of Psychiatry, Szeged, Hungary.
Neurosci Lett. 2012 May 31;517(2):136-9. doi: 10.1016/j.neulet.2012.04.046. Epub 2012 Apr 25.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder with complex etiology and strong genetic predisposition. A number of investigations support the possible involvement of sigma non-opioid intracellular receptor 1 (SIGMAR1) in the pathophysiology of AD. We aimed to investigate the association between SIGMAR1 polymorphisms and late-onset AD, therefore we genotyped rs1799729 (GC-241-240TT) and rs1800866 (Q2P) in 322 Hungarian late-onset AD patients and 250 ethnically matched, elderly control individuals. The investigated polymorphisms were in nearly complete linkage disequilibrium resulting in the GC-Q and TT-P predominant haplotypes that were subjected to the statistical analyses. Our data demonstrates an association between the SIGMAR1 TT-P variant and the risk for developing AD (p=0.019), and a potential modest interaction effect (p=0.058) of the co-presence of the TT-P haplotype with apolipoprotein E4 allele on the risk for AD. Based on this mild significance, we could not fully support the hypothesis that TT-P haplotype in interaction with APOE E4 allele confers risk for developing AD.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，病因复杂，遗传易感性强。许多研究支持西格玛非阿片类细胞内受体 1（SIGMAR1）可能参与 AD 的病理生理学。我们旨在研究 SIGMAR1 多态性与晚发性 AD 的相关性，因此我们对 322 名匈牙利晚发性 AD 患者和 250 名种族匹配的老年对照个体的 rs1799729（GC-241-240TT）和 rs1800866（Q2P）进行了基因分型。研究的多态性几乎处于完全连锁不平衡状态，导致 GC-Q 和 TT-P 主要单倍型进行了统计分析。我们的数据表明，SIGMAR1 TT-P 变体与 AD 发病风险之间存在关联（p=0.019），并且 TT-P 单倍型与载脂蛋白 E4 等位基因共存的潜在适度相互作用效应（p=0.058）对 AD 的风险有影响。基于这种轻微的意义，我们不能完全支持 TT-P 单倍型与 APOE E4 等位基因相互作用赋予 AD 发病风险的假设。
