Top

Published in:

01-11-2008 | Alzheimer's Disease and Related Disorders - Original Article

Promoter polymorphisms modulating HSPA5 expression may increase susceptibility to Taiwanese Alzheimer’s disease

Authors: W.-C. Hsu, H.-K. Wang, L.-C. Lee, H.-C. Fung, J.-C. Lin, H.-P. Hsu, Y.-R. Wu, L.-S. Ro, F.-J. Hu, Y.-T. Chang, G.-J. Lee-Chen, C.-M. Chen

Published in: Journal of Neural Transmission | Issue 11/2008

Abstract

Endoplasmic reticulum (ER) chaperone heat shock 70 kDa protein 5 (HSPA5/GRP78) is known to be involved in the metabolism of amyloid precursor protein and neuronal death in Alzheimer’s disease (AD) could arise from dysfunction of the ER. Through a case–control study and an expression assay, we investigated the association of HSPA5 −415 G/A (rs391957), −370 C/T (rs17840761) and −180 del/G (rs3216733) polymorphisms with Taiwanese AD. The overall genotype and allele frequency distribution at the completely linked −415 G/A and −180 del/G sites showed significant difference between AD cases and controls (P = 0.020 and 0.009, respectively). A decrease in risk of developing AD was demonstrated for −415 AA/−180 GG genotype [OR = 0.38, 95% confidence interval (CI) = 0.18–0.75, P = 0.007] and −415 A/−180 G allele (OR = 0.69, 95% CI = 0.51–0.91, P = 0.009). The HSPA5 transcriptional activity of the −415 A/−180 G allele was significantly lower than that of the −415 G/−180 del alleles, whereas induction of HSPA5 expression after ER stress was markedly increased in the cells with the −415 A/−180 G allele. Therefore, our preliminary results may suggest a protective role of the HSPA5 −415 A/−180 G allele in Taiwanese AD susceptibility.

Abecasis GR, Cookson WO (2000) GOLD-graphical overview of linkage disequilibrium. Bioinformatics 16:182–183PubMedCrossRef

Cheverud JM (2001) A simple correction for multiple comparisons in interval mapping genome scans. Heredity 87:52–58PubMedCrossRef

Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pericak-Vance MA (1993) Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 261:921–923PubMedCrossRef

Hardy J (1997) Amyloid, the presenilins and Alzheimer’s disease. Trends Neurosci 20:154–159PubMedCrossRef

Hoozemans JJ, Veerhuis R, Van Haastert ES, Rozemuller JM, Baas F, Eikelenboom P, Scheper W (2005) The unfolded protein response is activated in Alzheimer’s disease. Acta Neuropathol 110:165–172PubMedCrossRef

Hoshino T, Nakaya T, Araki W, Suzuki K, Suzuki T, Mizushima T (2007) Endoplasmic reticulum chaperones inhibit the production of amyloid-beta peptides. Biochem J 402:581–589PubMedCrossRef

Kakimura J, Kitamura Y, Takata K, Tsuchiya D, Taniguchi T, Gebicke-Haerter PJ, Smith MA, Perry G, Shimohama S (2002) Possible involvement of ER chaperone Grp78 on reduced formation of amyloid-beta deposits. Ann N Y Acad Sci 977:327–332PubMed

Kakiuchi C, Ishiwata M, Nanko S, Kunugi H, Minabe Y, Nakamura K, Mori N, Fujii K, Umekage T, Tochigi M, Kohda K, Sasaki T, Yamada K, Yoshikawa T, Kato T (2005) Functional polymorphisms of HSPA5: possible association with bipolar disorder. Biochem Biophys Res Commun 336:1136–1143PubMedCrossRef

Katayama T, Imaizumi K, Honda A, Yoneda T, Kudo T, Takeda M, Mori K, Rozmahel R, Fraser P, George-Hyslop PS, Tohyama M (2001) Disturbed activation of endoplasmic reticulum stress transducers by familial Alzheimer’s disease-linked presenilin-1 mutation. J Biol Chem 276:43446–43454PubMedCrossRef

Lee AS (2001) The glucose-regulated proteins: stress induction and clinical applications. Trends Biochem Sci 26:504–510PubMedCrossRef

Lee AS (2005) The ER chaperone and signaling regulator GRP78/BiP as a monitor of endoplasmic reticulum stress. Methods 35:373–381PubMedCrossRef

Li WW, Hsiung Y, Zhou Y, Roy B, Lee AS (1997) Induction of the mammalian GRP78/BiP gene by Ca²⁺ depletion and formation of aberrant proteins: activation of the conserved stress-inducible grp core promoter element by the human nuclear factor YY1. Mol Cell Biol 17:54–60PubMed

Marcus N, Green M (1997) NF-Y, a CCAAT box-binding protein, is one of the trans-acting factors necessary for the response of the murine ERp72 gene to protein traffic. DNA Cell Biol 16:1123–1131PubMedCrossRef

McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA work group under auspices of department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 34:934–944

Moroney JT, Bagiella E, Desmond DW, Hachinski VC, Mölsä PK, Gustafson L, Brun A, Fischer P, Erkinjuntti T, Rosen W, Paik MC, Tatemichi TK (1997) Meta-analysis of the Hachinski Ischemic Score in pathologically verified Dementias. Neurology 49:1096–1105PubMed

Nyholt DR (2004) A simple correction for multiple testing for singlenucleotide polymorphisms in linkage disequilibrium with each other. Am J Hum Genet 74:765–769PubMedCrossRef

Parker R, Phan T, Baumeister P, Roy B, Cheriyath V, Roy AL, Lee AS (2001) Identification of TFII-I as the endoplasmic reticulum stress response element binding factor ERSF: its autoregulation by stress and interaction with ATF6. Mol Cell Biol 21:3220–3233PubMedCrossRef

Sato N, Imaizumi K, Manabe T, Taniguchi M, Hitomi J, Katayama T, Yoneda T, Morihara T, Yasuda Y, Takagi T, Kudo T, Tsuda T, Itoyama Y, Makifuchi T, Fraser PE, St George-Hyslop P, Tohyama M (2001) Increased production of beta-amyloid and vulnerability to endoplasmic reticulum stress by an aberrant spliced form of presenilin 2. J Biol Chem 276:2108–2114PubMedCrossRef

Schröder M, Kaufman RJ (2005) ER stress and the unfolded protein response. Mutat Res 569:29–63PubMed

Stephens M, Smith NJ, Donnelly P (2001) A new statistical method for haplotype reconstruction from population data. Am J Hum Genet 68:978–989PubMedCrossRef

Wang HK, Fung HC, Hsu WC, Wu YR, Lin JC, Ro LS, Chang KH, Hwu FJ, Hsu Y, Huang SY, Lee-Chen GJ, Chen CM (2006) Apolipoprotein E, angiotensin-converting enzyme and kallikrein gene polymorphisms and the risk of Alzheimer’s disease and vascular dementia. J Neural Transm 113:1499–1509PubMedCrossRef

Yang Y, Turner RS, Gaut JR (1998) The chaperone BiP/GRP78 binds to amyloid precursor protein and decreases Abeta40 and Abeta42 secretion. J Biol Chem 273:25552–25555PubMedCrossRef

Yoshida H, Haze K, Yanagi H, Yura T, Mori K (1998) Identification of the cis-acting endoplasmic reticulum stress response element responsible for transcriptional induction of mammalian glucose-regulated proteins. Involvement of basic leucine zipper transcription factors. J Biol Chem 273:33741–33749PubMedCrossRef

Title: Promoter polymorphisms modulating HSPA5 expression may increase susceptibility to Taiwanese Alzheimer’s disease
Authors: W.-C. Hsu
H.-K. Wang
L.-C. Lee
H.-C. Fung
J.-C. Lin
H.-P. Hsu
Y.-R. Wu
L.-S. Ro
F.-J. Hu
Y.-T. Chang
G.-J. Lee-Chen
C.-M. Chen
Publication date: 01-11-2008
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 11/2008
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-008-0117-5

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Promoter polymorphisms modulating HSPA5 expression may increase susceptibility to Taiwanese Alzheimer’s disease

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 11/2008

Decreased M1 muscarinic receptor density in rat amphetamine model of schizophrenia is normalized by clozapine, but not haloperidol

Molecular genetics of adult ADHD: converging evidence from genome-wide association and extended pedigree linkage studies

Weight gain in children and adolescents during 45 weeks treatment with clozapine, olanzapine and risperidone

A longitudinal study of schizophrenia- and affective spectrum disorders in individuals diagnosed with a developmental language disorder as children

Baroreflex sensitivity and power spectral analysis in different extrapyramidal syndromes

Agmatine enhances the anticonvulsant action of phenobarbital and valproate in the mouse maximal electroshock seizure model