title: Functional polymorphisms of HSPA5: possible association with bipolar disorder.
abstract: Altered endoplasmic reticulum stress (ER) response signaling is suggested in bipolar disorder. Previously, we preliminarily reported the genetic association of HSPA5 (GRP78/BiP) with bipolar disorder. Here, we extended our analysis by increasing the number of Japanese case-control samples and NIMH Genetics Initiative bipolar trio samples (NIMH trios), and also analyzed schizophrenia samples. In Japanese, nominally significant association of one haplotype was observed in extended samples of bipolar disorder but not in schizophrenia. In NIMH trios, no association was found in total samples. However, an exploratory analysis suggested that the other haplotype was significantly over-transmitted to probands only from the paternal side. The associated haplotype in Japanese or NIMH pedigrees shared three common polymorphisms in the promotor, which was found to alter promotor activity. These findings suggested promotor polymorphisms of HSPA5 may affect the interindividual variability of ER stress response and may confer a genetic risk factor for bipolar disorder.
authors.affiliation: Laboratory for Molecular Dynamics of Mental Disorders, Brain Science Institute, RIKEN, Wako-shi, Saitama, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Kakiuchi
authors.forename: Mizuho
authors.initials: M
authors.lastname: Ishiwata
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Nanko
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kunugi
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Minabe
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakamura
authors.forename: Norio
authors.initials: N
authors.lastname: Mori
authors.forename: Kumiko
authors.initials: K
authors.lastname: Fujii
authors.forename: Tadashi
authors.initials: T
authors.lastname: Umekage
authors.forename: Mamoru
authors.initials: M
authors.lastname: Tochigi
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Kohda
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Sasaki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamada
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Tadafumi
authors.initials: T
authors.lastname: Kato
mesh_terms: D000328:Adult; D001483:Base Sequence; D001714:Bipolar Disorder / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones