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Significant Changes in the Tau A0 and A3 Alleles in Progressive Supranuclear Palsy and Improved Genotyping by Silver Detection
Rafael Oliva, MD, PhD;
Eduardo Tolosa, MD, PhD;
Mario Ezquerra, MS;
Jose Luis Molinuevo, MD;
Francesc Valldeoriola, MD;
Juan Burguera, MD;
Matilde Calopa, MD;
Marga Villa;
Francisca Ballesta, MD, PhD
Arch Neurol. 1998;55:1122-1124.
Background Progressive supranuclear palsy (PSP) is characterized by intraneuronal inclusions of neurofibrillary tangles formed by aggregated tau protein. A significant association between the tau gene A0/A0 genotype and PSP recently has been reported.
Objectives To determine if a significant association between the tau gene A0/A0 genotype and PSP could be found in an independent population with a genetic background different from that in which the initial association was reported, and to standardize a nonradioactive method for tau gene genotyping.
Setting Hospital and university research laboratories.
Subjects and Methods To facilitate genotyping of the tau gene, we standardized the conditions for silver-based detection of the tau gene dinucleotide polymorphism. Thirty patients from Spain clinically diagnosed as having probable PSP were included in the study and compared with different control groups.
Results A highly significant overrepresentation of the A0/A0 genotype (P<.001) and a decrease in the frequency of the A0/A3 genotype were found in the Spanish patients with PSP compared with the control group. A method based on silver detection was standardized for the genotyping of the tau gene.
Conclusions The detection of a significant association between the tau gene A0/A0 genotype and PSP in 2 independent populations rules out genetic stratification as an explanation for the association and indicates that the presence of the tau A0/A0 genotype is a risk factor for developing PSP independent of genetic background. Alternatively, the results could be interpreted as a protective effect of the A3 allele.
From the Genetics Service (Drs Oliva and Ballesta, Mr Ezquerra and Ms Villa), Institut de Investigacions Biomediques August Pi i Sonyer (IDIBAPS), and the Parkinson Disease and Movement Disorder Unit, Neurology Service (Drs Tolosa, Molinuevo, and Valldeoriola), Hospital Clínic i Provincial, Barcelona; the Neurology Service, Hospital La Fe, Valencia (Dr Burguera); and the Neurology Service, Hospital de Bellvitge, Hospitalet de Llobregat (Dr Calopa), Spain.
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