title: Association of six polymorphisms of the NOTCH4 gene with schizophrenia in the Japanese population.
abstract: The NOTCH4 gene is located at 6p21.3 and involved in the development and patterning of the central nervous systems. Recently, Wei and Hemmings [2000] observed that the gene was associated with schizophrenia. Subsequent to the report, several studies investigated the gene in schizophrenia, with controversial and inconclusive results. In the present study, we investigated six polymorphisms (SNPs 1-5 and a CTG repeat) of the gene in Japanese subjects with schizophrenia (n = 284) and the same number of controls. The polymorphisms include SNP5, which has been observed to be associated with schizophrenia in a Chinese population and two new SNPs 3-4 adjacent to SNP5, in addition to the SNPs 1-2 and the CTG repeat, which were suggested for the association with the disease in the previous study. As a result, no significant difference in genotypic distributions or allelic frequencies of the six polymorphisms of the gene was observed between the patients and the controls. Also, no significant difference was found in frequencies of haplotypes of the six polymorphisms between the patients and the controls. However, the distribution of SNP2 was significantly deviated from Hardy-Weinberg equilibrium in the patients (P = 0.000986), not in the controls, which could be a chance or due to an association of SNP2 with the disease. In conclusion, the present study provided no clear evidence for an association between the NOTCH4 gene and schizophrenia in the Japanese population.
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, 7-3-1Hongo, Bunkyo-ku, Tokyo 113, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Tochigi
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Tadashi
authors.initials: T
authors.lastname: Umekage
authors.forename: Jun
authors.initials: J
authors.lastname: Ohashi
authors.forename: Chieko
authors.initials: C
authors.lastname: Kato
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Marui
authors.forename: Takeshi
authors.initials: T
authors.lastname: Otowa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hibino
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Otani
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Kohda
authors.forename: Shuzheng
authors.initials: S
authors.lastname: Liu
authors.forename: Nobumasa
authors.initials: N
authors.lastname: Kato
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Sasaki
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002896:Chromosomes, Human, Pair 6; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface / Q000235:genetics*; D051880:Receptors, Notch; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics*; D018911:Trinucleotide Repeats
chemical_list: C106075:NOTCH4 protein, human; D011518:Proto-Oncogene Proteins; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface; D051880:Receptors, Notch