Lack of association between endoplasmic reticulum stress response genes and suicidal victims.

Published on Jan 1, 2007in The Kobe journal of the medical sciences
Kaoru Sakurai2
Estimated H-index: 2
(Kobe University),
Naoki Nishiguchi19
Estimated H-index: 19
(Kobe University)
+ 4 AuthorsYoshitake Hayashi45
Estimated H-index: 45
(Kobe University)
Sources
Abstract
As lithium has been shown to have a protective effect against suicidal behavior, genes on which mood stabilizers act may be involved in biological susceptibility to suicide. A recent study showed that endoplasmic reticulum (ER) stress response was impaired in the bipolar disorders and the impairment was ameliorated by a mood stabilizer, valproate. We hypothesized that an alteration of ER stress response is involved in the biological susceptibility to suicide through genetic polymorphisms, and examined the association of polymorphisms of X-box binding protein 1 (XBP1) and heat shock 70-kDa protein 5 (HSPA5) genes with suicide. We found no significant difference in the distribution of these polymorphisms between the suicide victims and the controls. These results suggest that the polymorphisms examined in this study are not involved in the susceptibility to suicide of the Japanese. Language: en
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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 bipol...
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We analyzed nine multigenerational families with ascertained affective spectrum disorders in northern Sweden's geographically isolated population of Vasterbotten. This northern Swedish population, which originated from a limited number of early settlers ∼8,000 years ago, is genetically more homogeneous than outbred populations. In a genomewide linkage analysis, we identified three chromosomal loci with multipoint LOD scores (MPLOD) ⩾2 at 9q31.1-q34.1 (MPLOD 3.24), 6q22.2-q24.2 (MPLOD 2.48), and ...
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Abstract Schizophrenia and bipolar disorder share some clinical features and linkage studies have shown that several loci are common. Recently, the authors found that the −116CG substitution in the promotor region of XBP1, a pivotal gene in endoplasmic reticulum (ER) stress response, causes the impairment of ER stress response, and that the −116C/C genotype is a protective factor; in other words the presence of the G allele increases the risk for bipolar disorder. The gene is located on 22q12.1,...
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Genes encoding proteins involved in serotonergic metabolism are major candidates in association studies of suicidal behavior. The tryptophan hydroxylase (TPH) gene, which codes for the rate-limiting enzyme of serotonin biosynthesis, is a major candidate gene and has been extensively studied in association studies of suicidal behavior, providing conflicting results. It is difficult to interpret these conflicting results due to lack of power, ethnic heterogeneity, and variations in the sampling st...
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The pathophysiology of bipolar disorder is still unclear, although family, twin and linkage studies implicate genetic factors 1 . Here we identified XBP1, a pivotal gene in the endoplasmic reticulum (ER) stress response, as contributing to the genetic risk factor for bipolar disorder. Using DNA microarray analysis of lymphoblastoid cells derived from two pairs of twins discordant with respect to the illness, we found downregulated expression of genes related to ER stress response in both affecte...
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