Synergistic effect of heme oxygenase-1 and tau genetic variants on Alzheimer's disease risk.
Oxidative stress plays a role in tau hyperphosphorylation and the development of neurofibrillary tangles (NFT). In Alzheimer's disease (AD) brain, accumulation of hyperphosphorylated tau in NFT is associated with the induction of heme oxygenase-1 (HO-1), a potent antioxidant that downregulates the production of tau. In a case-control study of 300 AD patients and 360 healthy controls, we examined whether the combined gene effects between HO-1 (-413, rs2071746) and tau (5' of exon 1, rs242557) polymorphisms might be responsible for susceptibility to AD. Subjects carrying both the HO-1 (-413) TT and the tau (5' of exon 1) AA genotypes had a more than 6.5-time higher risk of developing AD than subjects without these risk genotypes (OR = 6.65, 95% CI 1.12-39.29; p = 0.037). These data support a role for tau-related genes in the risk of AD.
Mateo
Ignacio
I
Neurology Service, University Hospital Marqués de Valdecilla, University of Cantabria, Santander, Spain.
Sánchez-Juan
Pascual
P
Rodríguez-Rodríguez
Eloy
E
Infante
Jon
J
Vázquez-Higuera
José Luis
JL
García-Gorostiaga
Inés
I
Berciano
José
J
Combarros
Onofre
O
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D005091:Exons / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D012307:Risk Factors; D016875:tau Proteins / Q000235:genetics*
D016875:tau Proteins; D051547:Heme Oxygenase-1