TY - JOUR
T1 - Functional polymorphisms of HSPA5
T2 - Possible association with bipolar disorder
AU - Kakiuchi, Chihiro
AU - Ishiwata, Mizuho
AU - Nanko, Shinichiro
AU - Kunugi, Hiroshi
AU - Minabe, Yoshio
AU - Nakamura, Kazuhiko
AU - Mori, Norio
AU - Fujii, Kumiko
AU - Umekage, Tadashi
AU - Tochigi, Mamoru
AU - Kohda, Kazuhisa
AU - Sasaki, Tsukasa
AU - Yamada, Kazuo
AU - Yoshikawa, Takeo
AU - Kato, Tadafumi
PY - 2005/11/4
Y1 - 2005/11/4
N2 - 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.
AB - 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.
KW - Association study
KW - Bipolar disorder
KW - Endoplasmic reticulum stress
KW - HSPA5/GRP78
KW - Promotor assay
KW - Schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=25644434771&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=25644434771&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2005.08.248
DO - 10.1016/j.bbrc.2005.08.248
M3 - Article
C2 - 16168956
AN - SCOPUS:25644434771
SN - 0006-291X
VL - 336
SP - 1136
EP - 1143
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -