Structural study of the microtubule-associated protein tau locus of Alzheimer's disease in Taiwan
Background: Haplotype structure of the microtubule-associated protein tau (MAPT) gene is associated with various tauopathies in the Caucasian population. With the knowledge that the association between MAPT structure and disease may be distinct in different ethnics, we intend to investigate the hapl...
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doaj-54eb87ae1f004ba1b9748d5ce3b93b652021-02-02T04:23:13ZengElsevierBiomedical Journal2319-41702320-28902014-06-0137312713210.4103/2319-4170.117891Structural study of the microtubule-associated protein tau locus of Alzheimer's disease in TaiwanChun-Wei Chang0Wen-Chuin Hsu1Alan Pittman2Yih-Ru Wu3John Hardy4Hon-Chung Fung5Department of Neurology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, TaiwanDepartment of Neurology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, TaiwanReta Lila Weston Institute of Neurological Studies, University College London, London, United KingdomDepartment of Neurology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, TaiwanDepartment of Molecular Neuroscience, Institute of Neurology, London, United KingdomDepartment of Neurology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, TaiwanBackground: Haplotype structure of the microtubule-associated protein tau (MAPT) gene is associated with various tauopathies in the Caucasian population. With the knowledge that the association between MAPT structure and disease may be distinct in different ethnics, we intend to investigate the haplotype structure of MAPT in Taiwanese and test it for association with Alzheimer's disease (AD). Methods: One hundred and eight AD patients and 108 sex- and-age matched healthy controls were recruited from the dementia outpatient clinic of Chang Gung Medical center. We genotyped the del-In9 marker that defines the extended H1 and H2 clades. We selected 21 single-nucleotide polymorphisms (SNPs) in the extended MAPT region from Japanese SNPs database and dbSNP database. Using the software TagIt, we analyzed the linkage disequilibrium structure of MAPT and compared the allele and genotype distribution between patient group and control group. Results: All the Taiwanese participants were H1 haplotypes. Linkage disequilibrium analysis showed the haplotype blocks in Taiwanese population had a smaller size in comparison to that of the Caucasian population. Single locus association showed significant p value in one of the tagging variants (rs242557) in our Taiwanese AD case-control cohorts. Conclusion: MAPT gene has four haplotype blocks in the Taiwanese population, each of around 40 kbp. In both European study and our study, the SNP rs242557 showed association with AD. Given the position of this SNP, the most possible explanation is that genetic variability in tau expression contributes to the risk of developing AD.http://www.biomedj.org/article.asp?issn=2319-4170;year=2014;volume=37;issue=3;spage=127;epage=132;aulast=Changalzheimer′s diseasehaplotypetautauopathy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chun-Wei Chang Wen-Chuin Hsu Alan Pittman Yih-Ru Wu John Hardy Hon-Chung Fung |
spellingShingle |
Chun-Wei Chang Wen-Chuin Hsu Alan Pittman Yih-Ru Wu John Hardy Hon-Chung Fung Structural study of the microtubule-associated protein tau locus of Alzheimer's disease in Taiwan Biomedical Journal alzheimer′s disease haplotype tau tauopathy |
author_facet |
Chun-Wei Chang Wen-Chuin Hsu Alan Pittman Yih-Ru Wu John Hardy Hon-Chung Fung |
author_sort |
Chun-Wei Chang |
title |
Structural study of the microtubule-associated protein tau locus of Alzheimer's disease in Taiwan |
title_short |
Structural study of the microtubule-associated protein tau locus of Alzheimer's disease in Taiwan |
title_full |
Structural study of the microtubule-associated protein tau locus of Alzheimer's disease in Taiwan |
title_fullStr |
Structural study of the microtubule-associated protein tau locus of Alzheimer's disease in Taiwan |
title_full_unstemmed |
Structural study of the microtubule-associated protein tau locus of Alzheimer's disease in Taiwan |
title_sort |
structural study of the microtubule-associated protein tau locus of alzheimer's disease in taiwan |
publisher |
Elsevier |
series |
Biomedical Journal |
issn |
2319-4170 2320-2890 |
publishDate |
2014-06-01 |
description |
Background: Haplotype structure of the microtubule-associated protein tau (MAPT) gene is associated with various tauopathies in the Caucasian population. With the knowledge that the association between MAPT structure and disease may be distinct in different ethnics, we intend to investigate the haplotype structure of MAPT in Taiwanese and test it for association with Alzheimer's disease (AD).
Methods: One hundred and eight AD patients and 108 sex- and-age matched healthy controls were recruited from the dementia outpatient clinic of Chang Gung Medical center. We genotyped the del-In9 marker that defines the extended H1 and H2 clades. We selected 21 single-nucleotide polymorphisms (SNPs) in the extended MAPT region from Japanese SNPs database and dbSNP database. Using the software TagIt, we analyzed the linkage disequilibrium structure of MAPT and compared the allele and genotype distribution between patient group and control group.
Results: All the Taiwanese participants were H1 haplotypes. Linkage disequilibrium analysis showed the haplotype blocks in Taiwanese population had a smaller size in comparison to that of the Caucasian population. Single locus association showed significant p value in one of the tagging variants (rs242557) in our Taiwanese AD case-control cohorts.
Conclusion: MAPT gene has four haplotype blocks in the Taiwanese population, each of around 40 kbp. In both European study and our study, the SNP rs242557 showed association with AD. Given the position of this SNP, the most possible explanation is that genetic variability in tau expression contributes to the risk of developing AD. |
topic |
alzheimer′s disease haplotype tau tauopathy |
url |
http://www.biomedj.org/article.asp?issn=2319-4170;year=2014;volume=37;issue=3;spage=127;epage=132;aulast=Chang |
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