Sakurai K, Migita O, Toru M, Arinami T
Department of Medical Genetics, Institute of Basic Medical Sciences, University of Tsukuba, 305-8575, Ibaraki, Japan.
Mol Psychiatry. 2002;7(4):412-5. doi: 10.1038/sj.mp.4000973.
Morphological alterations in the brains of schizophrenia patients suggest that neurodevelopmental dysfunction is involved in the etiology of the disease.(1) Such dysfunction may be due to functional alterations of cell adhesion molecules, which play important roles in cell migration, axonal growth, fasciculation, synaptogenesis, and synaptic remodeling. We screened for mutations in the coding region of the close homologue to L1 gene (CHL1), which is located on human chromosome 3p26, in 24 Japanese patients with schizophrenia. A missense polymorphism (Leu17Phe) in the signal peptide region was identified. A case-control comparison revealed significantly higher frequencies of the Leu/Leu genotype (P = 0.004) and the Leu allele (P = 0.006) in 282 Japanese schizophrenic patients than in 229 Japanese control subjects. The estimated odds ratio for schizophrenia was 1.83 (95% CI, 1.28-2.26) for the Leu/Leu genotype compared with the other genotypes. An association between this CHL1 gene polymorphism and schizophrenia supports the notion that cell adhesion molecules are involved in the etiology of schizophrenia.
精神分裂症患者大脑的形态学改变表明，神经发育功能障碍参与了该疾病的病因。(1) 这种功能障碍可能是由于细胞粘附分子的功能改变所致，细胞粘附分子在细胞迁移、轴突生长、成束、突触形成和突触重塑中起重要作用。我们对24名日本精神分裂症患者进行了筛查，检测位于人类染色体3p26上的L1基因紧密同源物（CHL1）编码区的突变。在信号肽区域发现了一个错义多态性（Leu17Phe）。病例对照比较显示，282名日本精神分裂症患者中Leu/Leu基因型（P = 0.004）和Leu等位基因（P = 0.006）的频率显著高于229名日本对照受试者。与其他基因型相比，Leu/Leu基因型患精神分裂症的估计比值比为1.83（95% CI，1.28 - 2.26）。这种CHL1基因多态性与精神分裂症之间的关联支持了细胞粘附分子参与精神分裂症病因的观点。
