Association between glycogen synthase kinase-3beta genetic polymorphism and late-onset Alzheimer's disease.
Aberrant phosphorylated tau is the major component of the neurofibrillary tangles in Alzheimer's disease (AD) brains. Glycogen synthase kinase-3beta (GSK-3beta) phosphorylates tau protein, and increased GSK-3beta expression has been associated with neurofibrillary tangles. Saitohin (STH) is a recently identified protein that shares tissue expression pattern with tau, and previous evidence in the Spanish population indicated that a polymorphism at codon 7 (Q7R) of the STH gene was associated with late-onset AD. Since both GSK-3beta and STH are related to tau, we examined the association between a polymorphism in the promoter region (-50) of the GSK-3beta gene and AD, either through an independent effect or through interaction with the STH (Q7R) polymorphism, in a well-defined group of 333 sporadic AD patients and 307 control subjects from Spain. The current study reveals that GSK-3beta (-50) TT genotype is associated with an increased risk (OR 1.99, p = 0.003) for late-onset (after the age of 72 years) AD. Our results indicate that both the GSK-3beta (-50) and STH (Q7R) polymorphisms increase the risk of late-onset (subjects >72 years) AD, although they appear to be independent and thus not to interact synergistically.
Mateo
Ignacio
I
Neurology Service, Marqués de Valdecilla University Hospital (University of Cantabria), Santander, Spain.
Infante
Jon
J
Llorca
Javier
J
Rodríguez
Eloy
E
Berciano
José
J
Combarros
Onofre
O
D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D002391:Catchment Area, Health; D003062:Codon / Q000235:genetics; D005260:Female; D005838:Genotype; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D013030:Spain / Q000453:epidemiology; D016875:tau Proteins / Q000235:genetics
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D003062:Codon; C458340:STH protein, human; D016875:tau Proteins; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3