Association between the extended tau haplotype and frontotemporal dementia.
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.
Verpillat
Patrice
P
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
Camuzat
Agnès
A
Hannequin
Didier
D
Thomas-Anterion
Catherine
C
Puel
Michèle
M
Belliard
Serge
S
Dubois
Bruno
B
Didic
Mira
M
Michel
Bernard-François
BF
Lacomblez
Lucette
L
Moreaud
Olivier
O
Sellal
François
F
Golfier
Véronique
V
Campion
Dominique
D
Clerget-Darpoux
Françoise
F
Brice
Alexis
A
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*
D016875:tau Proteins