Tau haplotypes regulate transcription and are associated with Parkinson's disease

Kwok, J. B. J., Teber, E. T., Loy, C., Hallupp, M., Nicholson, G., Mellick, G. D., Buchanan, D. D., Silburn, P. A. and Schofield, P. R. (2004) Tau haplotypes regulate transcription and are associated with Parkinson's disease. Annals of Neurology, 55 3: 329-334. doi:10.1002/ana.10826

Author Kwok, J. B. J.
Teber, E. T.
Loy, C.
Hallupp, M.
Nicholson, G.
Mellick, G. D.
Buchanan, D. D.
Silburn, P. A.
Schofield, P. R.
Title Tau haplotypes regulate transcription and are associated with Parkinson's disease
Journal name Annals of Neurology   Check publisher's open access policy
ISSN 0364-5134
Publication date 2004-01-01
Sub-type Article (original research)
DOI 10.1002/ana.10826
Volume 55
Issue 3
Start page 329
End page 334
Total pages 6
Editor R. T. Johnson
Place of publication USA
Publisher John Wiley & Sons Inc
Language eng
Subject C1
321013 Neurology and Neuromuscular Diseases
730104 Nervous system and disorders
Abstract A primary haplotype (H1) of the microtubule-associated protein Tau (MAPT) gene is associated with Parkinson's disease (PD). However, the mechanism for disease susceptibility remains unknown. We examined the promoter region of MAPT and identified single nucleotide polymorphisms and insertions of 1 to 11 nucleotides. These polymorphisms corresponded to the previously characterized haplotypes, H1 and H2, as well as a novel variant of the H1 haplotype, H1'. As observed in other studies, we demonstrated a significant association with the H1/H1 promoter genotype and PD in a cohort of 206 idiopathic late-onset cases. This is in contrast with a panel of 13 early-onset PD patients, for whom we did not detect any mutations in MAPT. By examining single nucleotide polymorphisms in adjacent genes, we showed that linkage disequilibrium does not extend beyond the MAPT haplotype to neighboring genes. To define the mechanism of disease susceptibility, we examined the transcriptional activity of the promoter haplotypes using a luciferase reporter assay. We demonstrated in two human cell lines, SK-N-MC and 293, that the H1 haplotype was more efficient at driving gene expression than the H2 haplotype. Our data suggest that an increase in expression of the MAPT gene is a susceptibility factor in idiopathic PD.
Keyword Clinical Neurology
Progressive Supranuclear Palsy
Lewy Bodies
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2005 Higher Education Research Data Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 116 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 15 Aug 2007, 13:31:42 EST