title: The H2 MAPT haplotype is associated with familial frontotemporal dementia.
abstract: There is now considerable evidence that the gene encoding for tau protein (MAPT) is implicated in frontotemporal dementia (FTD). The role of MAPT haplotypes in neurodegenerative diseases has been suggested, but their contribution in familial dementia has not been extensively investigated. Here, we investigated (1) the association between the MAPT haplotypes and sporadic (sFTD) or familial FTD (FFTD) (controls n = 99, sFTD n = 53, FFTD n = 50), (2) the interactive effect between MAPT haplotypes and APOE gene. We found an overrepresentation of H2 haplotype (OR = 1.83, P = 0.029) and of H2H2 genotype in FFTD patients (OR = 6.09, P = 0.007). This association was even stronger in APOE e4 negatives FFTD (H2: OR = 2.9, P = 0.001; H2H2: OR = 12.67, P = 0.001). Our results support idea that the MAPT H2 haplotype is a risk factor for FFTD. This locus could contain this or other inheritable genetic determinants contributing to increase risk of developing dementia.
authors.affiliation: NeuroBioGen Lab-Memory Clinic, IRCCS Centro San Giovanni di Dio-Fatebenefratelli, via Pilastroni 4, 25125 Brescia, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Ghidoni
authors.forename: Simona
authors.initials: S
authors.lastname: Signorini
authors.forename: Laura
authors.initials: L
authors.lastname: Barbiero
authors.forename: Elena
authors.initials: E
authors.lastname: Sina
authors.forename: Paola
authors.initials: P
authors.lastname: Cominelli
authors.forename: Aldo
authors.initials: A
authors.lastname: Villa
authors.forename: Luisa
authors.initials: L
authors.lastname: Benussi
authors.forename: Giuliano
authors.initials: G
authors.lastname: Binetti
mesh_terms: D000368:Aged; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D004252:DNA Mutational Analysis; D003704:Dementia / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D012307:Risk Factors; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D016875:tau Proteins