Uchida Naohiko, Ujike Hiroshi, Tanaka Yuji, Sakai Ayumu, Yamamoto Mitsutoshi, Fujisawa Yoshikatsu, Kanzaki Akihiro, Kuroda Shigetoshi
Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Shikata-cho 2-5-1, Okayama 700-8558, Japan.
Am J Geriatr Psychiatry. 2005 Dec;13(12):1062-6. doi: 10.1176/appi.ajgp.13.12.1062.
Some preclinical evidence suggests that the sigma receptor type 1, which plays several roles in learning and memory, may also be involved in the pathogenesis of Alzheimer disease (AD). The authors provide here genetic evidence that the sigma receptor type 1 (SIGMAR1) gene is involved in susceptibility to AD.
Two polymorphisms of the SIGMAR1 gene, G-241T/C-240T and Q2P, were analyzed in a Japanese sample of 239 patients with AD and 227 comparisons subjects. These two polymorphisms were in complete linkage disequilibrium with each other, resulting in only two haplotypes, GC-241-240Q2 and TT-241-240P2.
There was a significant association between AD and the TT-241-240P2 haplotype of the SIGMAR1 gene and its homozygote, found with late-onset, but not early-onset AD. After stratification by epsilon4 allele status of the apolipoprotein E gene, TT-241-240P2 homozygosity of the SIGMAR1 gene reduced the risk of AD in epsilon4 allele carriers by three-fourths.
The present study suggests that the TT-241-240P2 haplotype of the SIGMAR1 gene, which decreases expression of the gene, may have a protective role against susceptibility to AD.
一些临床前证据表明，在学习和记忆中发挥多种作用的1型sigma受体可能也参与了阿尔茨海默病（AD）的发病机制。作者在此提供遗传学证据，表明1型sigma受体（SIGMAR1）基因与AD易感性有关。
在一个由239例AD患者和227例对照受试者组成的日本样本中，分析了SIGMAR1基因的两个多态性，即G-241T/C-240T和Q2P。这两个多态性彼此完全连锁不平衡，仅产生两种单倍型，即GC-241-240Q2和TT-241-240P2。
AD与SIGMAR1基因的TT-241-240P2单倍型及其纯合子之间存在显著关联，这种关联在晚发型AD中发现，但早发型AD中未发现。按载脂蛋白E基因的ε4等位基因状态分层后，SIGMAR1基因的TT-241-240P2纯合性使ε4等位基因携带者患AD的风险降低了四分之三。
本研究表明，SIGMAR1基因的TT-241-240P2单倍型可降低该基因的表达，可能对AD易感性具有保护作用。
