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Journal of Human Genetics

, Volume 52, Issue 10, pp 794–803 | Cite as

Association analysis of HSP90B1 with bipolar disorder

  • Chihiro Kakiuchi
  • Mizuho Ishiwata
  • Shinichiro Nanko
  • Hiroshi Kunugi
  • Yoshio Minabe
  • Kazuhiko Nakamura
  • Norio Mori
  • Kumiko Fujii
  • Tadashi Umekage
  • Mamoru Tochigi
  • Kazuhisa Kohda
  • Tsukasa Sasaki
  • Kazuo Yamada
  • Takeo Yoshikawa
  • Tadafumi Kato
Original Article
  • 102 Downloads

Abstract

Pathophysiological role of endoplasmic reticulum (ER) stress response signaling has been suggested for bipolar disorder. The goal of this study was to test the genetic association between bipolar disorder and an ER chaperone gene, HSP90B1 (GRP94/gp96), which is located on a candidate locus, 12q23.3. We tested the genetic association between bipolar disorder and HSP90B1 by case-control studies in two independent Japanese sample sets and by a transmission disequilibrium test (TDT) in NIMH Genetics initiative bipolar trio samples (NIMH trios). We also performed gene expression analysis of HSP90B1 in lymphoblastoid cells. Among the 11 SNPs tested, rs17034977 showed significant association in both Japanese sample sets. The frequency of the SNP was lower in NIMH samples than in Japanese samples and there was no significant association in NIMH trios. Gene expression analysis of HSP90B1 in lymphoblastoid cells suggested a possible relationship between the associated SNP and mRNA levels. HSP90B1 may have a pathophysiological role in bipolar disorder in the Japanese population, though further study will be needed to understand the underlying functional mechanisms.

Keywords

Bipolar disorder HSP90B1/GRP94/gp96 Association study Evi12 Endoplasmic reticulum stress Retrovirus 

Notes

Acknowledgments

This research was supported by a grant for Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, a Grant-in-Aid from Japanese Ministry of Health and Labor, and a Grant-in-Aid from the Japanese Ministry of Education, Culture, Sports, Science and Technology. The authors declare no conflict of interest.

References

  1. Argon Y, Simen BB (1999) GRP94, an ER chaperone with protein and peptide binding properties. Semin Cell Dev Biol 10:495–505PubMedCrossRefGoogle Scholar
  2. Arinami T, Ohtsuki T, Ishiguro H, Ujike H, Tanaka Y, Morita Y et al (2005) Genomewide high-density SNP linkage analysis of 236 Japanese families supports the existence of schizophrenia susceptibility loci on chromosomes 1p, 14q, and 20p. Am J Hum Genet 77:937–944PubMedCrossRefGoogle Scholar
  3. Bando Y, Katayama T, Aleshin AN, Manabe T, Tohyama M (2004) GRP94 reduces cell death in SH-SY5Y cells perturbated calcium homeostasis. Apoptosis 9:501–508PubMedCrossRefGoogle Scholar
  4. Bown C, Wang JF, MacQueen G, Young LT (2000) Increased temporal cortex ER stress proteins in depressed subjects who died by suicide. Neuropsychopharmacology 22:327–332PubMedCrossRefGoogle Scholar
  5. Cichon S, Buervenich S, Kirov G, Akula N, Dimitrova A, Green E et al (2004) Lack of support for a genetic association of the XBP1 promoter polymorphism with bipolar disorder in probands of European origin. Nat Genet 36:783–784, author reply 784–785PubMedCrossRefGoogle Scholar
  6. Curtis D, Kalsi G, Brynjolfsson J, McInnis M, O’Neill J, Smyth C et al (2003) Genome scan of pedigrees multiply affected with bipolar disorder provides further support for the presence of a susceptibility locus on chromosome 12q23-q24, and suggests the presence of additional loci on 1p and 1q. Psychiatr Genet 13:77–84PubMedCrossRefGoogle Scholar
  7. Dawson E, Parfitt E, Roberts Q, Daniels J, Lim L, Sham P et al (1995) Linkage studies of bipolar disorder in the region of the Darier’s disease gene on chromosome 12q23–24.1. Am J Med Genet 60:94–102PubMedCrossRefGoogle Scholar
  8. Detera-Wadleigh SD, Badner JA, Berrettini WH, Yoshikawa T, Goldin LR, Turner G et al (1999) A high-density genome scan detects evidence for a bipolar-disorder susceptibility locus on 13q32 and other potential loci on 1q32 and 18p11.2. Proc Natl Acad Sci USA 96:5604–5609PubMedCrossRefGoogle Scholar
  9. Dow GS, Hudson TH, Vahey M, Koenig ML (2003) The acute neurotoxicity of mefloquine may be mediated through a disruption of calcium homeostasis and ER function in vitro. Malar J 2:14PubMedCrossRefGoogle Scholar
  10. Dow GS, Caridha D, Goldberg M, Wolf L, Koenig ML, Yourick DL, Wang Z (2005) Transcriptional profiling of mefloquine-induced disruption of calcium homeostasis in neurons in vitro. Genomics 86:539–550PubMedCrossRefGoogle Scholar
  11. Ekholm JM, Kieseppa T, Hiekkalinna T, Partonen T, Paunio T, Perola M et al (2003) Evidence of susceptibility loci on 4q32 and 16p12 for bipolar disorder. Hum Mol Genet 12:1907–1915PubMedCrossRefGoogle Scholar
  12. Even C, Friedman S, Lanouar K (2001) Bipolar disorder after mefloquine treatment. J Psychiatry Neurosci 26:252–253PubMedGoogle Scholar
  13. Ewald H, Degn B, Mors O, Kruse TA (1998) Significant linkage between bipolar affective disorder and chromosome 12q24. Psychiatr Genet 8:131–140PubMedCrossRefGoogle Scholar
  14. Green E, Elvidge G, Jacobsen N, Glaser B, Jones I, O’Donovan MC et al (2005) Localization of bipolar susceptibility locus by molecular genetic analysis of the chromosome 12q23-q24 region in two pedigrees with bipolar disorder and Darier’s disease. Am J Psychiatry 162:35–42PubMedCrossRefGoogle Scholar
  15. Hiroi T, Wei H, Hough C, Leeds P, Chuang DM (2005) Protracted lithium treatment protects against the ER stress elicited by thapsigargin in rat PC12 cells: roles of intracellular calcium, GRP78 and Bcl-2. Pharmacogenomics J 5:102–111PubMedCrossRefGoogle Scholar
  16. Hou SJ, Yen FC, Cheng CY, Tsai SJ, Hong CJ (2004) X-box binding protein 1 (XBP1) C–116G polymorphisms in bipolar disorders and age of onset. Neurosci Lett 367:232–234PubMedCrossRefGoogle Scholar
  17. Jayanthi S, Deng X, Noailles PA, Ladenheim B, Cadet JL (2004) Methamphetamine induces neuronal apoptosis via cross-talks between endoplasmic reticulum and mitochondria-dependent death cascades. Faseb J 18:238–251PubMedCrossRefGoogle Scholar
  18. Jurata LW, Bukhman YV, Charles V, Capriglione F, Bullard J, Lemire AL et al (2004) Comparison of microarray-based mRNA profiling technologies for identification of psychiatric disease and drug signatures. J Neurosci Methods 138:173–188PubMedCrossRefGoogle Scholar
  19. Kakiuchi C, Iwamoto K, Ishiwata M, Bundo M, Kasahara T, Kusumi I et al (2003) Impaired feedback regulation of XBP1 as a genetic risk factor for bipolar disorder. Nat Genet 35:171–175PubMedCrossRefGoogle Scholar
  20. Kakiuchi C, Ishiwata M, Nanko S, Kunugi H, Minabe Y, Nakamura K et al (2005) Functional polymorphisms of HSPA5: possible association with bipolar disorder. Biochem Biophys Res Commun 336:1136–1143PubMedCrossRefGoogle Scholar
  21. Kakiuchi C, Ishiwata M, Hayashi A, Kato T (2006) XBP1 induces WFS1 through an endoplasmic reticulum stress response element-like motif in SH-SY5Y cells. J Neurochem 97:545–555PubMedCrossRefGoogle Scholar
  22. Kakiuchi C, Ishiwata M, Nanko S, Kunugi H, Minabe Y, Nakamura K et al (2007) Association analysis of ATF4 and ATF5, genes for interacting-proteins of DISC1, in bipolar disorder. Neurosci Lett 417:316–321PubMedCrossRefGoogle Scholar
  23. Kato T (2007) Molecular genetics of bipolar disorder and depression. Psychiatry Clin Neurosci 61:3–19PubMedCrossRefGoogle Scholar
  24. Kato T, Ishiwata M, Mori K, Washizuka S, Tajima O, Akiyama T, Kato N (2003) Mechanisms of altered Ca2+ signalling in transformed lymphoblastoid cells from patients with bipolar disorder. Int J Neuropsychopharmacol 6:379–389PubMedCrossRefGoogle Scholar
  25. Kim AJ, Shi Y, Austin RC, Werstuck GH (2005) Valproate protects cells from ER stress-induced lipid accumulation and apoptosis by inhibiting glycogen synthase kinase-3. J Cell Sci 118:89–99PubMedCrossRefGoogle Scholar
  26. Manji HK, Duman RS (2001) Impairments of neuroplasticity and cellular resilience in severe mood disorders: implications for the development of novel therapeutics. Psychopharmacol Bull 35:5–49PubMedGoogle Scholar
  27. Maziade M, Roy MA, Chagnon YC, Cliche D, Fournier JP, Montgrain N et al (2005) Shared and specific susceptibility loci for schizophrenia and bipolar disorder: a dense genome scan in Eastern Quebec families. Mol Psychiatry 10:486–499PubMedCrossRefGoogle Scholar
  28. Morissette J, Villeneuve A, Bordeleau L, Rochette D, Laberge C, Gagne B et al (1999) Genome-wide search for linkage of bipolar affective disorders in a very large pedigree derived from a homogeneous population in quebec points to a locus of major effect on chromosome 12q23-q24. Am J Med Genet 88:567–587PubMedCrossRefGoogle Scholar
  29. Nigam SK, Goldberg AL, Ho S, Rohde MF, Bush KT, Sherman M (1994) A set of endoplasmic reticulum proteins possessing properties of molecular chaperones includes Ca(2+)-binding proteins and members of the thioredoxin superfamily. J Biol Chem 269:1744–1749PubMedGoogle Scholar
  30. Schroder M, Kaufman RJ (2005) ER stress and the unfolded protein response. Mutat Res 569:29–63PubMedGoogle Scholar
  31. Shao L, Sun X, Xu L, Young LT, Wang JF (2006) Mood stabilizing drug lithium increases expression of endoplasmic reticulum stress proteins in primary cultured rat cerebral cortical cells. Life Sci 78:1317–1323PubMedCrossRefGoogle Scholar
  32. Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E et al (1998) The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 59(Suppl 20):22–33, quiz 34–57PubMedGoogle Scholar
  33. So J, Warsh JJ, Li PP (2007) Impaired endoplasmic reticulum stress response in B-lymphoblasts from patients with bipolar-I disorder. Biol Psychiatry 62:141–147PubMedCrossRefGoogle Scholar
  34. Stranger BE, Forrest MS, Dunning M, Ingle CE, Beazley C, Thorne N et al (2007) Relative impact of nucleotide and copy number variation on gene expression phenotypes. Science 315:848–853PubMedCrossRefGoogle Scholar
  35. Toda H, Suzuki G, Nibuya M, Shioda K, Nishijima K, Wakizono T et al (2006) Behavioral stress and activated serotonergic neurotransmission induce XBP-1 splicing in the rat brain. Brain Res 1112:26–32PubMedCrossRefGoogle Scholar
  36. Valk PJ, Vankan Y, Joosten M, Jenkins NA, Copeland NG, Lowenberg B, Delwel R (1999) Retroviral insertions in Evi12, a novel common virus integration site upstream of Tra1/Grp94, frequently coincide with insertions in the gene encoding the peripheral cannabinoid receptor Cnr2. J Virol 73:3595–3602PubMedGoogle Scholar
  37. van den Akker E, Vankan-Berkhoudt Y, Valk PJ, Lowenberg B, Delwel R (2005) The common viral insertion site Evi12 is located in the 5’-noncoding region of Gnn, a novel gene with enhanced expression in two subclasses of human acute myeloid leukemia. J Virol 79:5249–5258PubMedCrossRefGoogle Scholar
  38. Wang JF, Bown C, Young LT (1999) Differential display PCR reveals novel targets for the mood-stabilizing drug valproate including the molecular chaperone GRP78. Mol Pharmacol 55:521–527PubMedGoogle Scholar
  39. Wang JF, Azzam JE, Young LT (2003) Valproate inhibits oxidative damage to lipid and protein in primary cultured rat cerebrocortical cells. Neuroscience 116:485–489PubMedCrossRefGoogle Scholar
  40. Yamada K, Nakamura K, Minabe Y, Iwayama-Shigeno Y, Takao H, Toyota T et al (2004) Association analysis of FEZ1 variants with schizophrenia in Japanese cohorts. Biol Psychiatry 56:683–690PubMedCrossRefGoogle Scholar
  41. Yoshida H (2004) Molecular biology of the ER stress response. Seikagaku 76:617–630PubMedGoogle Scholar

Copyright information

© The Japan Society of Human Genetics and Springer 2007

Authors and Affiliations

  • Chihiro Kakiuchi
    • 1
  • Mizuho Ishiwata
    • 1
  • Shinichiro Nanko
    • 2
  • Hiroshi Kunugi
    • 3
  • Yoshio Minabe
    • 4
  • Kazuhiko Nakamura
    • 5
  • Norio Mori
    • 5
  • Kumiko Fujii
    • 6
  • Tadashi Umekage
    • 7
  • Mamoru Tochigi
    • 1
    • 8
  • Kazuhisa Kohda
    • 9
  • Tsukasa Sasaki
    • 7
  • Kazuo Yamada
    • 10
  • Takeo Yoshikawa
    • 10
  • Tadafumi Kato
    • 1
  1. 1.Laboratory for Molecular Dynamics of Mental DisordersRIKEN Brain Science InstituteWakoJapan
  2. 2.Department of Psychiatry and Genome Research CenterTeikyo University School of MedicineTokyoJapan
  3. 3.Department of Mental Disorder Research, National Institute of NeuroscienceNational Center of Neurology and PsychiatryTokyoJapan
  4. 4.Department of Psychiatry and NeurobiologyKanazawa University Graduate School of Medical ScienceKanazawaJapan
  5. 5.Department of PsychiatryHamamatsu University School of MedicineHamamatsuJapan
  6. 6.Department of PsychiatryShiga University of Medical ScienceOtsuJapan
  7. 7.Department of Psychiatry, Health Service CenterUniversity of TokyoTokyoJapan
  8. 8.Department of Neuropsychiatry, Faculty of MedicineUniversity of TokyoTokyoJapan
  9. 9.Department of PhysiologyKeio University School of MedicineTokyoJapan
  10. 10.Laboratory for Molecular PsychiatryRIKEN Brain Science InstituteWakoJapan

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