Identification of a novel polymorphism in the promoter region of the tau gene highly associated to progressive supranuclear palsy in humans

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 potenti al changes in the promoter region of the tau gene that could further extend the previously described haplotype. The tau promoter region was analyzed t hrough single strand conformation polymorphism followed by direct sequencin g in PSP patients (n = 35), in controls (n = 195) and in Alzheimer's diseas e (AD; n = 74) patients. We have been able to identify a G to C change at p osition -221 of the tau gene promoter region. The CC genotype has been dete cted to be present with a significantly higher frequency in PSP patients (9 1.4%; P < 0.00001; OR = 11.8), but not in AD patients, as compared with con trols (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 addit ion to extending the previously described haplotype associated to PSP, this -221 G to C change is an interesting candidate that could provide a potent ial explanation for the association of the haplotype to increased risk for developing PSP. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.