Ishiguro H, Koga M, Horiuchi Y, Inada T, Iwata N, Ozaki N, Ujike H, Muratake T, Someya T, Arinami T
Department of Medical Genetics, Doctoral Program in Social and Environmental Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan.
Neurosci Res. 2007 Jun;58(2):145-8. doi: 10.1016/j.neures.2007.02.008. Epub 2007 Feb 20.
The protein interacting with C-kinase 1 (PICK1) has been implicated in the susceptibility to schizophrenia. PICK1 interacts with enzymes and receptors that play roles in the pathogenesis of schizophrenia via glutamatergic dysfunction. Recently, two studies reported associations between schizophrenia and two PICK1 gene polymorphisms, rs3952 in Chinese and Japanese populations and rs2076369 in a Japanese population. We attempted to confirm these associations in a case-control study of 1765 Japanese patients with schizophrenia and 1851 Japanese control subjects. Neither polymorphism was associated with schizophrenia (rs3952, p=0.755; rs2076369, p=0.997). A haplotype block with these polymorphisms spanning the 5' region of the PICK1 gene showed high linkage disequilibrium in the Japanese population (D'=0.98, r(2)=0.34); however, neither haplotype was significantly associated with schizophrenia. We conclude that the common haplotypes and polymorphisms of the PICK1 gene identified thus far are unlikely to contribute to genetic susceptibility to schizophrenia in the Japanese population.
与C激酶1相互作用的蛋白（PICK1）被认为与精神分裂症易感性有关。PICK1与通过谷氨酸能功能障碍在精神分裂症发病机制中起作用的酶和受体相互作用。最近，两项研究报道了精神分裂症与两个PICK1基因多态性之间的关联，在中国和日本人群中为rs3952，在日本人群中为rs2076369。我们试图在一项包含1765名日本精神分裂症患者和1851名日本对照受试者的病例对照研究中证实这些关联。这两种多态性均与精神分裂症无关（rs3952，p = 0.755；rs2076369，p = 0.997）。在日本人群中，一个包含这些多态性且跨越PICK1基因5'区域的单倍型块显示出高连锁不平衡（D' = 0.98，r² = 0.34）；然而，两种单倍型均与精神分裂症无显著关联。我们得出结论，迄今为止所确定的PICK1基因常见单倍型和多态性不太可能导致日本人群中精神分裂症的遗传易感性。
