title: Association between the extended tau haplotype and frontotemporal dementia.
abstract: 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.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  Neurology departments of 12 French university hospitals.
  
  
  METHODS
  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.
authors.affiliation: Département d'Epidémiologie, de Biostatistique, et de Recherche Clinique, Hôpital Bichat-Claude Bernard, 46 rue Henri Huchard, 75877 Paris CEDEX 18, France. patrice.verpillat@bch.ap-hop-paris.fr
authors.forename: Patrice
authors.initials: P
authors.lastname: Verpillat
authors.forename: Agnès
authors.initials: A
authors.lastname: Camuzat
authors.forename: Didier
authors.initials: D
authors.lastname: Hannequin
authors.forename: Catherine
authors.initials: C
authors.lastname: Thomas-Anterion
authors.forename: Michèle
authors.initials: M
authors.lastname: Puel
authors.forename: Serge
authors.initials: S
authors.lastname: Belliard
authors.forename: Bruno
authors.initials: B
authors.lastname: Dubois
authors.forename: Mira
authors.initials: M
authors.lastname: Didic
authors.forename: Bernard-François
authors.initials: BF
authors.lastname: Michel
authors.forename: Lucette
authors.initials: L
authors.lastname: Lacomblez
authors.forename: Olivier
authors.initials: O
authors.lastname: Moreaud
authors.forename: François
authors.initials: F
authors.lastname: Sellal
authors.forename: Véronique
authors.initials: V
authors.lastname: Golfier
authors.forename: Dominique
authors.initials: D
authors.lastname: Campion
authors.forename: Françoise
authors.initials: F
authors.lastname: Clerget-Darpoux
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D016001:Confidence Intervals; D003704:Dementia / Q000235:genetics*; D005260:Female; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D016875:tau Proteins / Q000235:genetics*
chemical_list: D016875:tau Proteins