Interaction of α-synuclein and tau genotypes in Parkinson's disease

被引：34

作者：

Mamah, CE

Lesnick, TG

Lincoln, SJ

Strain, KJ

de Andrade, M

Bower, JH

Ahlskog, JE

Rocca, WA

Farrer, MJ

Maraganore, DM

机构：

[1] Mayo Clin, Coll Med, Dept Neurol, Rochester, MN 55905 USA

[2] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN 55905 USA

[3] Mayo Clin, Coll Med, Dept Neurosci, Jacksonville, FL 32224 USA

来源：

ANNALS OF NEUROLOGY | 2005年 / 57卷 / 03期

关键词：

D O I：

10.1002/ana.20387

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

To determine whether the microtubule-associated protein tau (MAPT) and a-synuclein (SNCA) genes interact to confer Parkinson's disease (PD) susceptibility, we conducted a study of 557 case-control pairs. There was an increased risk of PD for persons with either SNCA 261/261 or MAPT H1/H1 genotypes as compared with persons with neither (odds ratio, 1.96; 95% confidence interval, 1.34-2.86; p = 0.0003). However, the combined effect of the two genotypes was the same as for either of the genotypes alone (separate and equal). These findings are consistent with in vitro experiments that revealed tau-mediated fibrillization of a-synuclein protein at low concentrations (dose threshold effect).

引用

收藏

页码：439 / 443

页数：5

相关论文

共 20 条

[1] NEW LOOK AT STATISTICAL-MODEL IDENTIFICATION [J].

AKAIKE, H .

IEEE TRANSACTIONS ON AUTOMATIC CONTROL, 1974, AC19 (06) :716-723

[2] Association of an extended haplotype in the tau gene with progressive supranuclear palsy [J].

Baker, M ;

Litvan, I ;

Houlden, H ;

Adamson, J ;

Dickson, D ;

Perez-Tur, J ;

Hardy, J ;

Lynch, T ;

Bigio, E ;

Hutton, M .

HUMAN MOLECULAR GENETICS, 1999, 8 (04) :711-715

[3] Incidence and distribution of parkinsonism in Olmsted County, Minnesota, 1976-1990 [J].

Bower, JH ;

Maraganore, DM ;

McDonnell, SK ;

Rocca, WA .

NEUROLOGY, 1999, 52 (06) :1214-1220

[4] Functional analysis of intra-allelic variation at NACP-Rep1 in the α-synuclein gene [J].

Chiba-Falek, O ;

Touchman, JW ;

Nussbaum, RL .

HUMAN GENETICS, 2003, 113 (05) :426-431

[5] Concurrence of α-synuclein and tau brain pathology in the Contursi kindred [J].

Duda, JE ;

Giasson, BI ;

Mahon, ME ;

Miller, DC ;

Golbe, LI ;

Lee, VMY ;

Trojanowski, JQ .

ACTA NEUROPATHOLOGICA, 2002, 104 (01) :7-11

[6] α-synuclein gene haplotypes are associated with Parkinson's disease [J].

Farrer, M ;

Maraganore, DM ;

Lockhart, P ;

Singleton, A ;

Lesnick, TG ;

de Andrade, M ;

West, A ;

de Silva, R ;

Hardy, J ;

Hernandez, D .

HUMAN MOLECULAR GENETICS, 2001, 10 (17) :1847-1851

[7] Initiation and synergistic fibrillization of tau and alpha-synuclein [J].

Giasson, BI ;

Forman, MS ;

Higuchi, M ;

Golbe, LI ;

Graves, CL ;

Kotzbauer, PT ;

Trojanowski, JQ ;

Lee, VMY .

SCIENCE, 2003, 300 (5619) :636-640

[8]

KNOWLER WC, 1988, AM J HUM GENET, V43, P520

[9] Ala30Pro mutation in the gene encoding α-synuclein in Parkinson's disease [J].

Krüger, R ;

Kuhn, W ;

Müller, T ;

Woitalla, D ;

Graeber, M ;

Kösel, S ;

Przuntek, H ;

Epplen, JT ;

Schöls, L ;

Riess, O .

NATURE GENETICS, 1998, 18 (02) :106-108

[10] Tau haplotypes regulate transcription and are associated with Parkinson's disease [J].

Kwok, JBJ ;

Teber, ET ;

Loy, C ;

Hallupp, M ;

Nicholson, G ;

Mellick, GD ;

Buchanan, DD ;

Silburn, PA ;

Schofield, PR .

ANNALS OF NEUROLOGY, 2004, 55 (03) :329-334