TY - JOUR
T1 - 5′-upstream variants of CRHR1 and MAPT genes associated with age at onset in progressive supranuclear palsy and cortical basal degeneration
AU - Cruchaga, Carlos
AU - Vidal-Taboada, Jose M.
AU - Ezquerra, Mario
AU - Lorenzo, Elena
AU - Martinez-Lage, Pablo
AU - Blazquez, Marta
AU - Tolosa, Eduardo
AU - Pastor, Pau
AU - Gaig, Carles
AU - Marti, Maria Jose
AU - Molinuevo, Jose Luis
AU - Valldeoriola, Francesc
AU - Campdelacreu, Jaume
AU - Masdeuf, Joseph C.
AU - Luquín, Rosario
AU - Obesof, Jose A.
AU - Pastor, Maria A.
AU - Riverol, Mario
AU - Rodriguezf, Maria C.
AU - Villoslada, Pablo
AU - Tuñon, Teresa
AU - Huerta, Cecilia
AU - Alvarez, Victoria
AU - Calopa, Matilde
AU - Erro, Elena
AU - Rojo, Ana
AU - Ruiz, Javier
N1 - Funding Information:
This work was supported by grant “ Ayudas para la Realización de Proyectos de Investigación ” 2006–2007 Government of Navarra, Spain to PP, grant 2007SRG00387 Generalitat de Catalunya, Spain and by the award “ Distinció per la promoció de la Recerca Universitària Generalitat de Catalunya ”, Spain, both to ET. CC is a Government of Navarra Postdoctoral Fellow (2005–2007).
PY - 2009/2/1
Y1 - 2009/2/1
N2 - Two different H1 sub-haplotypes at chromosome 17q21, H1C and H1E′A, have been associated with progressive supranuclear palsy (PSP) and cortical basal degeneration (CBD). We analyzed the SNPs included in the H1C and H1E′A haplotypes in a large Spanish PSP/CBD series and their interaction with age at onset (AAO). Survival analysis of rs1880753 marker was consistently associated with disease risk and with an earlier age at onset under an additive model. Its location at 160 kb and 50 kb upstream of tau and CRHR1 genes, respectively, suggests that it might act as a cis-element that regulates gene expression. Rs45502095H1was also associated with AAO under a recessive model. Haplotype analysis failed to replicate the association of H1C and H1E′A haplotypes with PSP/CBD. However, we found a strong association of two H1 sub-haplotypes with PSP and CBD (H1E′C and H1Q), which include MAPT and CRHR1 genes where the risk variant for PSP/CBD could lie.
AB - Two different H1 sub-haplotypes at chromosome 17q21, H1C and H1E′A, have been associated with progressive supranuclear palsy (PSP) and cortical basal degeneration (CBD). We analyzed the SNPs included in the H1C and H1E′A haplotypes in a large Spanish PSP/CBD series and their interaction with age at onset (AAO). Survival analysis of rs1880753 marker was consistently associated with disease risk and with an earlier age at onset under an additive model. Its location at 160 kb and 50 kb upstream of tau and CRHR1 genes, respectively, suggests that it might act as a cis-element that regulates gene expression. Rs45502095H1was also associated with AAO under a recessive model. Haplotype analysis failed to replicate the association of H1C and H1E′A haplotypes with PSP/CBD. However, we found a strong association of two H1 sub-haplotypes with PSP and CBD (H1E′C and H1Q), which include MAPT and CRHR1 genes where the risk variant for PSP/CBD could lie.
KW - Age at onset
KW - Cortical basal degeneration
KW - Haplotype
KW - Microtubule-associated protein tau
KW - Progressive supranuclear palsy
UR - http://www.scopus.com/inward/record.url?scp=58249104270&partnerID=8YFLogxK
U2 - 10.1016/j.nbd.2008.09.027
DO - 10.1016/j.nbd.2008.09.027
M3 - Article
C2 - 19022385
AN - SCOPUS:58249104270
VL - 33
SP - 164
EP - 170
JO - Neurobiology of Disease
JF - Neurobiology of Disease
SN - 0969-9961
IS - 2
ER -