Ishiguro H, Ohtsuki T, Toru M, Itokawa M, Aoki J, Shibuya H, Kurumaji A, Okubo Y, Iwawaki A, Ota K, Shimizu H, Hamaguchi H, Arinami T
Department of Medical Genetics, Institute of Basic Medical Science, University of Tsukuba, Ibaraki, Japan.
Neurosci Lett. 1998 Nov 20;257(1):45-8. doi: 10.1016/s0304-3940(98)00797-6.
Several antipsychotic agents such as haloperidol and rimcazole are known to bind to sigma receptors with high affinity, and evidence for a potential link between sigma receptors and the etiology of schizophrenia has been reported. The present study was conducted to systematically search for nucleotide variants of the type 1 sigma receptor gene in 48 schizophrenics. Two polymorphisms were found: GC-241-240TT in the 5' flanking region and Gln2Pro. These two polymorphisms were in nearly complete linkage disequilibrium with each other. The Pro2 variant of the Gln2Pro polymorphism changes the endoplasmic reticulum retention signal motif. These polymorphisms were examined in an extended sample of schizophrenics (n = 308) and controls (n = 433) and a significant association between the presence of the TT/Pro2 haplotype and schizophrenia was observed (odds ratio = 1.27, P = 0.04).
已知几种抗精神病药物，如氟哌啶醇和利木唑，能以高亲和力与σ受体结合，并且有报道称σ受体与精神分裂症病因之间存在潜在联系的证据。本研究旨在系统搜索48名精神分裂症患者中1型σ受体基因的核苷酸变异。发现了两种多态性：5'侧翼区的GC-241-240TT和Gln2Pro。这两种多态性彼此几乎完全连锁不平衡。Gln2Pro多态性的Pro2变体改变了内质网滞留信号基序。在精神分裂症患者（n = 308）和对照（n = 433）的扩展样本中检查了这些多态性，观察到TT/Pro2单倍型的存在与精神分裂症之间存在显著关联（优势比 = 1.27，P = 0.04）。
