Is There Any Influence of TBP CAG / CAA Repeats on Huntington's Disease Age at Onset?

Abstract Huntington's disease (HD) is a genetic neurodegenerative progressive and fatal disease characterized by motor disorder, cognitive impairment and behavioral problems, caused by expanded repeats of CAG trinucleotides in the HTT gene. The aim of this study was to investigate the influence of TBP gene CAG/CAA repeats in conjunction with HTT gene CAG repeats, on the age of HD onset in Brazilian individuals. Individuals diagnosed as molecularly negative for HD, presented 29-39 TBP CAG/CAA (mean = 36 ± 2; median = 36). The most frequent allele had 36 repeats. The heterozygosity was 84%. In individuals diagnosed as molecularly positive for HD, a range of 25-40 TBP CAG/ CAA was found (mean = 36 ± 2; median = 36). The most frequent TBP allele had 38 repeats and the heterozygosity was 81%. We also conducted TBP direct Sanger sequencing of some samples which demonstrated other TBP structures different from the wild-type. The HTT expanded CAG and TBP CAG/CAA repeat sizes jointly explained 66% of the age at onset (AO) in our HD patients. The strongest variable in the model associated to AO was the number of expanded HTT CAG repeats. The difference between the association of HD AO with HTT expanded CAG together with TBP CAG / CAA and the association of HD AO with HTT expanded CAG was 0.001 (∆R2). Therefore, we found a weak association (0.1%) of TBP CAG/CAA repeats on HD AO, if any.