No evidence of proteins containing long polyglutamine tracts in the pathogenesis of bipolar disorder
Turecki G., Aida M., Grof P., Joober R., Cavazzoni P., Duffy A., Grof E., Ahrens B., Berghöfer A., Müller-Oerlinghausen B., Dvoráková M., Libigerová E., Vojtechovský M., Zvolský P., Nilsson A., Prochazka H., Licht RW., Rasmussen NA., Schou M., Vestergaard P., Holzinger A., Schumann C., Thau K., Rouleau GA.
Recent studies have reported anticipation in bipolar families, suggesting that trinucleotide repeats may have a role in the etiology of bipolar disorder. This hypothesis has been further supported by a number of studies using the repeat expansion detection (RED) method, which have shown increased genomic content of CAG repeats in bipolar patients as compared to normal control subjects. As CAG triplets are translated into glutamine, our aim was to test for the presence of proteins with expanded polyglutamine tracts in bipolar patients. Using Western blot analysis with a monoclonal antibody (1C2) that detects proteins containing polyglutamine tracts, we investigated lymphoblastoid cell lines from 70 bipolar patients and 73 normal controls. In order to test a more homogeneous sample, we studied patients who respond well to lithium as described in detail in Grof et al. [J Affect Disord 32:85-95, 1994). There was no evidence of specific immunoreactive bands among bipolar patients. Our results do not support the hypothesis that translated CAG repeats play a major role in the pathogenesis of bipolar disorder.