Functional polymorphisms of HSPA5: Possible association with bipolar disorder
Functional polymorphisms of HSPA5: Possible association with bipolar disorder
复制标题
DOI：
10.1016/j.bbrc.2005.08.248
复制
发表时间：
2005-11-04
影响因子：
3.1
通讯作者：
Kato, T
中科院分区：
文献类型：
--
作者：
Kakiuchi, C;Ishiwata, M;Kato, T
内质网应激（ER）反应信号的改变可能与双相情感障碍有关。此前，我们初步报道了HSPA5 （GRP78/BiP）与双相情感障碍的遗传关联。在这里，我们通过增加日本病例对照样本和NIMH遗传学倡议双相三重奏样本（NIMH三重奏）的数量来扩展我们的分析，并分析了精神分裂症样本。在日本，在双相情感障碍的扩展样本中观察到一种单倍型的名义上的显著关联，但在精神分裂症中没有。在NIMH三人组中，在所有样本中没有发现关联。然而，一项探索性分析表明，其他单倍型仅从父系侧显着过度传递给先证者。日本或NIMH家系的相关单倍型在启动子上有三个共同的多态性，这被发现改变了启动子的活性。这些发现表明HSPA5的启动子多态性可能影响内质网应激反应的个体间变异性，并可能赋予双相情感障碍的遗传危险因素。(c) 2005爱思唯尔公司版权所有。
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.(c) 2005 Elsevier Inc. All rights reserved.