title: Identification of a novel polymorphism in the promoter region of the tau gene highly associated to progressive supranuclear palsy in humans.
abstract: An intronic polymorphism and other changes in the transcribed region of the tau gene forming a haplotype have been previously described associated to progressive supranuclear palsy (PSP). These results raised the possibility that a change at or near the tau gene could be responsible for an increased risk to develop PSP. We initiated the present work in research for potential changes in the promoter region of the tau gene that could further extend the previously described haplotype. The tau promoter region was analyzed through single strand conformation polymorphism followed by direct sequencing in PSP patients (n = 35), in controls (n = 195) and in Alzheimer's disease (AD; n = 74) patients. We have been able to identify a G to C change at position -221 of the tau gene promoter region. The CC genotype has been detected to be present with a significantly higher frequency in PSP patients (91.4%; P < 0.00001; OR = 11.8), but not in AD patients, as compared with controls (49.74%). Subsequently we have detected that the CC -221 tau promoter genotype is significantly associated to the tau intronic A0/A0 genotype (P < 0.00001). The detected -221 tau G to C change occurs within a potential c-myb proto-oncogene element present in the promoter region. Thus, in addition to extending the previously described haplotype associated to PSP, this -221 G to C change is an interesting candidate that could provide a potential explanation for the association of the haplotype to increased risk for developing PSP.
authors.affiliation: Genetics Service, Hospital Clínic i Provincial, Faculty of Medicine, University of Barcelona, Institut d'lnvestigacions Biomèdiques August Pi y Sunyer, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Ezquerra
authors.forename: P
authors.initials: P
authors.lastname: Pastor
authors.forename: F
authors.initials: F
authors.lastname: Valldeoriola
authors.forename: J L
authors.initials: JL
authors.lastname: Molinuevo
authors.forename: R
authors.initials: R
authors.lastname: Blesa
authors.forename: E
authors.initials: E
authors.lastname: Tolosa
authors.forename: R
authors.initials: R
authors.lastname: Oliva
mesh_terms: D001483:Base Sequence; D016384:Consensus Sequence; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007438:Introns; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics; D012307:Risk Factors; D013494:Supranuclear Palsy, Progressive / Q000235:genetics*; D014158:Transcription, Genetic; D016875:tau Proteins / Q000235:genetics*
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D020598:Proto-Oncogene Proteins c-myb; D016875:tau Proteins