TY - JOUR
T1 - Dementia risk in parkinson disease: Disentangling the role of MAPT Haplotypes
AU - Setó-Salvia, Núria
AU - Clarimón, Jordi
AU - Pagonabarraga, Javier
AU - Pascual-Sedano, Berta
AU - Campolongo, Antonia
AU - Combarros, Onofre
AU - Mateo, Jose Ignacio
AU - Regaña, Daniel
AU - Martínez-Corral, Merce
AU - Marquié, Marta
AU - Alcolea, Daniel
AU - Suárez-Calvet, Marc
AU - Molina-Porcel, Laura
AU - Dols, Oriol
AU - Gómez-Isla, Teresa
AU - Blesa, Rafael
AU - Lleó, Alberto
AU - Kulisevsky, Jaime
PY - 2011/3/1
Y1 - 2011/3/1
N2 - Background: Dementia in Parkinson disease (PD) causes nursing home placement, caregiver distress, higher health care burden, and increased mortality. Objective: To determine whether the microtubule-associated protein tau (MAPT) H1 haplotype and MAPT subhaplotypes play a role in the risk of PD and Parkinson disease-dementia (PDD) complex. Design: Case-control genetic analysis. Setting: Movement Disorders and Memory Units, Hospital de Sant Pau, Barcelona, Spain. Participants: Two hundred two patients with PD (48 of whom developed dementia >2 years after disease onset), 41 patients with Lewy body dementia (LBD, pathologically confirmed in 17), 164 patients with Alzheimer disease (AD), and 374 controls. Methods: The MAPT haplotype was determined by testing for a 238-base pair deletion between exons 9 and 10, which is characteristic of the H2 haplotype. Haploview was used to visualize linkage disequilibrium relationships between all genetic variants (5 single-nucleotide polymorphisms and the del-In9 variant) within and surrounding the MAPT region. Results: The H1 haplotype was significantly overrepresented in PD patients compared with controls (P = .001). Stratifying the PD sample by the presence of dementia revealed a stronger association in PDD patients (sex- and age-adjusted odds ratio, 3.73; P = .002) than in PD patients without dementia (sex- and age-adjusted odds ratio, 1.89; P = .04). Examination of specific subhaplotypes showed that a rare version of the H1 haplotype (named H1p) was overrepresented in PDD patients compared with controls (2.3% vs 0.1%; P = .003). No positive signals for any of the MAPT variants or H1 subhaplotypes were found in AD or LBD. Conclusions: Our data confirm that MAPT H1 is associated with PD and has a strong influence on the risk of dementia in PD patients. Our results also suggest that none of the MAPT subhaplotypes play a significant role in other neurodegenerative diseases, such as LBD or AD. ©2011 American Medical Association. All rights reserved.
AB - Background: Dementia in Parkinson disease (PD) causes nursing home placement, caregiver distress, higher health care burden, and increased mortality. Objective: To determine whether the microtubule-associated protein tau (MAPT) H1 haplotype and MAPT subhaplotypes play a role in the risk of PD and Parkinson disease-dementia (PDD) complex. Design: Case-control genetic analysis. Setting: Movement Disorders and Memory Units, Hospital de Sant Pau, Barcelona, Spain. Participants: Two hundred two patients with PD (48 of whom developed dementia >2 years after disease onset), 41 patients with Lewy body dementia (LBD, pathologically confirmed in 17), 164 patients with Alzheimer disease (AD), and 374 controls. Methods: The MAPT haplotype was determined by testing for a 238-base pair deletion between exons 9 and 10, which is characteristic of the H2 haplotype. Haploview was used to visualize linkage disequilibrium relationships between all genetic variants (5 single-nucleotide polymorphisms and the del-In9 variant) within and surrounding the MAPT region. Results: The H1 haplotype was significantly overrepresented in PD patients compared with controls (P = .001). Stratifying the PD sample by the presence of dementia revealed a stronger association in PDD patients (sex- and age-adjusted odds ratio, 3.73; P = .002) than in PD patients without dementia (sex- and age-adjusted odds ratio, 1.89; P = .04). Examination of specific subhaplotypes showed that a rare version of the H1 haplotype (named H1p) was overrepresented in PDD patients compared with controls (2.3% vs 0.1%; P = .003). No positive signals for any of the MAPT variants or H1 subhaplotypes were found in AD or LBD. Conclusions: Our data confirm that MAPT H1 is associated with PD and has a strong influence on the risk of dementia in PD patients. Our results also suggest that none of the MAPT subhaplotypes play a significant role in other neurodegenerative diseases, such as LBD or AD. ©2011 American Medical Association. All rights reserved.
U2 - 10.1001/archneurol.2011.17
DO - 10.1001/archneurol.2011.17
M3 - Article
VL - 68
SP - 359
EP - 364
IS - 3
ER -