This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (29)  • Contact me when this article is cited  Related Content  • Related article  • Similar articles in this journal  Topic Collections  • Dementias  • Neurogenetics  • Genetic Disorders  • Alert me on articles by topic  Social Bookmarking   What's this?

Patrice Verpillat, MD; Agnès Camuzat, BS; Didier Hannequin, MD; Catherine Thomas-Anterion, MD; Michèle Puel, MD; Serge Belliard, MD; Bruno Dubois, MD; Mira Didic, MD; Bernard-François Michel, MD; Lucette Lacomblez, MD; Olivier Moreaud, MD; François Sellal, MD; Véronique Golfier, MD; Dominique Campion, MD, PhD; Françoise Clerget-Darpoux, PhD; Alexis Brice, MD

Arch Neurol. 2002;59:935-939.

Background  Recent studies have shown an association between an extended tau haplotype (H1) that covers the entire human tau gene and progressive supranuclear palsy or, more inconsistently, other neurodegenerative disorders, such as corticobasal degeneration, Parkinson disease, Alzheimer disease, and frontotemporal dementia (FTD). In addition, disease-causing mutations in the tau gene on chromosome 17 have been detected in some families with autosomal dominant FTD and parkinsonism. In FTD, the pathological accumulation of the microtubule-associated protein tau suggests that the tau gene may be a genetic risk factor for this disorder.

Objective  To confirm or refute the association between the H1 haplotype or the H1H1 genotype of the tau gene and FTD.

Design  Case-control study.

Setting  Neurology departments of 12 French university hospitals.

Participants  One hundred unrelated patients with FTD and 79 controls.

Methods  Tau genotype (contiguous polymorphisms in exons 1, 7, and 13 and in intron 9 used to reconstruct the extended haplotypes H1 and H2). Clinical examination, psychometric testing, laboratory tests, computed tomography and magnetic resonance imaging, single-photon emission computed tomography, and electroencephalography for patients with FTD.

Results  The H1H1 genotype was significantly overrepresented in patients with FTD compared with controls (62% vs 46%; P = .01, 1-sided; odds ratio adjusted for age and sex, 1.95). After stratification according to apolipoprotein E (APOE) genotype, we found a significant interaction between APOE and tau genotypes (P = .03).

Conclusions  This study of the largest series of patients with FTD confirms the primary role of tau in FTD and establishes that the H1 haplotype of the tau gene and the E2 allele of APOE interact by an unknown mechanism that increases the risk of FTD.

From Institut National de la Santé et de la Recherche Médicale (INSERM) U535, Le Kremlin Bicêtre (Drs Verpillat and Clerget-Darpoux); the Department of Epidemiology and Biostatistics, University Hospital Bichat-Claude Bernard, Assistance Publique–Hôpitaux de Paris (AP-HP)/University Paris VII, Paris (Dr Verpillat); INSERM U289, University Hospital Salpêtrière, Paris (Drs Verpillat and Brice and Ms Camuzat); INSERM Equipe Propre Inserm (EPI) 9906, Rouen (Drs Hannequin and Campion); the Department of Neurology, University Hospital, Rouen (Dr Hannequin); the Department of Neurology, University Hospital, Saint-Etienne (Dr Thomas-Anterion); the Department of Neurology, University Hospital Purpan, Toulouse (Dr Puel); the Department of Neurology, University Hospital Pontchaillou, Rennes (Drs Belliard and Golfier); the Department of Neurology, University Hospital Salpêtrière, Paris (Dr Dubois); the Department of Neurology and Neuropsychology, University Hospital Timone, Marseille (Dr Didic); INSERM Equipe Mixte Inserm (EMI) U9926, Marseille (Dr Didic); the Department of Neurology, University Hospital Sainte-Marguerite, Marseille (Dr Michel); the Federation of Neurology Mazarin and the Department of Pharmacology (Dr Lacomblez) and the Department of Genetics, Cytogenetics and Embryology (Dr Brice), University Hospital Salpêtrière, Paris; the Department of Neurology, University Hospital, Grenoble (Dr Moreaud); and the Department of Neurology, University Hospital, Strasbourg (Dr Sellal), France.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

RELATED ARTICLE

Archives of Neurology Reader's Choice: Continuing Medical Education
Arch Neurol. 2002;59(6):1048-1050.
FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Association of the Tau Haplotype H2 With Age at Onset and Functional Alterations of Glucose Utilization in Frontotemporal Dementia
Laws et al.
Am. J. Psychiatry 2007;164:1577-1584.
ABSTRACT | FULL TEXT  

Association Between Tau H2 Haplotype and Age at Onset in Frontotemporal Dementia
Borroni et al.
Arch Neurol 2005;62:1419-1422.
ABSTRACT | FULL TEXT  

Genetic aspects of Alzheimer's disease, Pick's disease, and other dementias
Nee et al.
AM J ALZHEIMERS DIS OTHER DEMEN 2004;19:219-225.
ABSTRACT  

Association of polymorphisms in the Tau and Saitohin genes with Parkinson's disease
Levecque et al.
J. Neurol. Neurosurg. Psychiatry 2004;75:478-480.
ABSTRACT | FULL TEXT  

Medical and environmental risk factors for sporadic frontotemporal dementia: a retrospective case-control study
Rosso et al.
J. Neurol. Neurosurg. Psychiatry 2003;74:1574-1576.
ABSTRACT | FULL TEXT