title: Association and synergistic interaction between promoter variants of the DRD4 gene in Japanese schizophrenics.
abstract: Recent association studies suggest that polymorphisms in the promoter and exon 1 upstream region of the dopamine D4 receptor (DRD4) gene play a functional role in the development of common psychiatric illnesses, although there are also conflicting results. In this study, we re-sequenced this region to identify all genomic variants, and tested them for association with schizophrenia. A total of 570 Japanese schizophrenic cases with matched controls were studied by genotyping all identified/validated common polymorphisms (-1106T>C, -906T>C, -809G>A, -616G>C, -521T>C, -376C>T, -291C>T and 12-bp repeat) and a known microsatellite (120-bp tandem duplication) in the upstream region. A single nucleotide polymorphism (SNP) -809G>A in the promoter region was found to be significantly associated with disease (P=0.018 and 0.032 for allelic and genotypic comparisons, respectively), although not surviving after Bonferroni correction. Logistic regression analysis showed that a combination of the four polymorphisms, -809G>A, -616G>C, -291C>T and the 12-bp repeat, conferred a susceptibility to schizophrenia. These results suggest that the upstream variants have a primary functional effect in the etiology of schizophrenia in the Japanese population.
authors.affiliation: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-city, Saitama, 351-0198, Japan.|Department of Paediatrics, Tokyo Medical University, Shinjuku, Tokyo, 160-0023, Japan.
authors.forename: Mizuho
authors.initials: M
authors.lastname: Nakajima
authors.affiliation: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-city, Saitama, 351-0198, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Hattori
authors.affiliation: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-city, Saitama, 351-0198, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-city, Saitama, 351-0198, Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Iwayama
authors.affiliation: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-city, Saitama, 351-0198, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Toyota
authors.affiliation: Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, 431-3192, Japan.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Iwata
authors.affiliation: Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, 431-3192, Japan.
authors.forename: Kenji J
authors.initials: KJ
authors.lastname: Tsuchiya
authors.affiliation: Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, 431-3192, Japan.
authors.forename: Genichi
authors.initials: G
authors.lastname: Sugihara
authors.affiliation: Division of Clinical Neuroscience, Chiba University, Center for Forensic Mental Health, Chiba, 260-8670, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Hashimoto
authors.affiliation: Department of Psychiatry, Chiba University, Graduate School of Medicine, Chiba, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Department of Psychiatry, Chiba University, Graduate School of Medicine, Chiba, Japan.
authors.forename: Masaomi
authors.initials: M
authors.lastname: Iyo
authors.affiliation: Department of Paediatrics, Tokyo Medical University, Shinjuku, Tokyo, 160-0023, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Hoshika
authors.affiliation: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-city, Saitama, 351-0198, Japan. takeo@brain.riken.jp.|CREST, Japan Science and Technology Agency, Saitama, Japan. takeo@brain.riken.jp.
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D005091:Exons; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007564:Japan; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics*
chemical_list: C493599:DRD4 protein, human; D050638:Receptors, Dopamine D4