title: Association study of polymorphisms in the 5' upstream region of human DISC1 gene with schizophrenia.
abstract: Disrupted-in-Schizophrenia-1 (DISC1) is a gene in which a mutant truncation by a balanced t(1;11)(p42.1;q14.3) translocation is segregated with major psychiatric illness with a predominance of schizophrenic symptomatology in a large Scottish family. However, no functional polymorphisms have been detected that are associated with schizophrenia in general populations. As prior polymorphism searches in DISC1 have been focused on coding exons and flanking introns, the present study examined sequence variations in the 5' upstream region of DISC1. Screening of exon 1 through to approximately 1.0 kb upstream of exon 1 identified 6 polymorphisms, including 2 novel variants, -94C>A and -199(CG)(n). We tested these variants for associations with schizophrenia in the first set of a case (n = 198) and control (n = 198) panel, and found significant results with -274G>C (genotypic P = 0.01) and -215(TG)(n) (genotypic P = 0.039). However, we failed to replicate these associations in a second, larger independent patient (n = 532) and control (n = 519) sample. These results suggest that the genomic interval of DISC1 probably involved in transcriptional regulation does not display major genetic relevance in Japanese schizophrenia patients.
authors.affiliation: Department of Schizophrenia Research, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya, Tokyo 156-8585, Japan.
authors.forename: Thessa T J P
authors.initials: TT
authors.lastname: Kockelkorn
authors.forename: Makoto
authors.initials: M
authors.lastname: Arai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Norishige
authors.initials: N
authors.lastname: Fukuda
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamada
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Minabe
authors.forename: Tomoko
authors.initials: T
authors.lastname: Toyota
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ujike
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sora
authors.forename: Norio
authors.initials: N
authors.lastname: Mori
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Masanari
authors.initials: M
authors.lastname: Itokawa
mesh_terms: D024506:5' Flanking Region / Q000235:genetics*; D000483:Alleles; D000595:Amino Acid Sequence; D004247:DNA / Q000235:genetics; D017931:DNA Primers; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: C412476:DISC1 protein, human; D017931:DNA Primers; D009419:Nerve Tissue Proteins; D004247:DNA