title: ITIH3 polymorphism may confer susceptibility to psychiatric disorders by altering the expression levels of GLT8D1.
abstract: A recent genome-wide analysis indicated that a polymorphism (rs2535629) of ITIH3 showed the strongest association signal with susceptibility to psychiatric disorders in Caucasian populations. The aim of the study was to replicate the association of rs2535629 with schizophrenia and major depressive disorder (MDD) in Japanese subjects. A total of 611 patients with schizophrenia, 868 with MDD, and 1193 healthy controls were successfully genotyped for rs2535629. A significant difference in allele distribution was found between patients with schizophrenia and controls (odds ratio [OR] = 1.21, 95% confidence interval [CI]: 1.05-1.39, P = 0.0077). A similar trend was found for patients with MDD (OR = 1.11, 95% CI: 0.98-1.26, P = 0.092). The allele distribution in the combined patient group (schizophrenia and MDD) was significantly different from that of the control group (OR = 1.15, 95% CI: 1.03-1.28, P = 0.011). Gene expression microarray analysis of whole blood samples in 39 MDD patients and 40 healthy controls showed that rs2535629 has a strong influence on the expression levels of ITIH4 and GLT8D1. The expression levels of GLT8D1 were significantly higher in patients with MDD than in controls (P = 0.021). To our knowledge, the present study showed for the first time the association of rs2535629 with psychiatric disorders in an Asian population. Our findings suggest that rs2535629 influences the susceptibility to psychiatric disorders by affecting the expression level of GLT8D1.
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1, Ogawahigashi, Kodaira, Tokyo, 187-8502, Japan; Department of Psychiatry, Shinshu University School of Medicine, Matsumoto, Nagano, 390-8621, Japan.
authors.forename: Daimei
authors.initials: D
authors.lastname: Sasayama
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1, Ogawahigashi, Kodaira, Tokyo, 187-8502, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hori
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1, Ogawahigashi, Kodaira, Tokyo, 187-8502, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: DNA Chip Research Inc., Yokohama, Kanagawa, 230-0045, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1, Ogawahigashi, Kodaira, Tokyo, 187-8502, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Teraishi
authors.affiliation: Department of Occupational Therapy, School of Nursing and Rehabilitation Sciences, Show University, Tokyo, 142-8555, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tatsumi
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1, Ogawahigashi, Kodaira, Tokyo, 187-8502, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Hattori
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1, Ogawahigashi, Kodaira, Tokyo, 187-8502, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Ota
authors.affiliation: National Center of Neurology and Psychiatry, Kodaira, Tokyo, 187-8502, Japan.
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Higuchi
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1, Ogawahigashi, Kodaira, Tokyo, 187-8502, Japan. Electronic address: hkunugi@ncnp.go.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kunugi
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D001798:Blood Proteins / Q000235:genetics*; D003865:Major Depressive Disorder / Q000097:blood* / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006023:Glycoproteins / Q000097:blood / Q000235:genetics*; D016695:Glycosyltransferases / Q000097:blood*; D006801:Humans; D007564:Japan; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D011110:Polymorphism, Genetic; D053491:Proteinase Inhibitory Proteins, Secretory / Q000097:blood / Q000235:genetics*; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy / Q000235:genetics*; D012720:Severity of Illness Index
chemical_list: D001798:Blood Proteins; D006023:Glycoproteins; C091236:ITIH4 protein, human; D053491:Proteinase Inhibitory Proteins, Secretory; C000592012:GLT8D1 protein, human; D016695:Glycosyltransferases
keywords: GLT8D1; Gene expression; ITIH3; ITIH4; Major depressive disorder; Microarray; Schizophrenia; Single nucleotide polymorphism