Trinucleotide repeat expansion in the β1 subunit of the sodium pump in manic-depression illness: a negative study

Background: Trinucleotide repeats have become a recognized molecular abnormality in a variety of neuropsychiatric conditions. Bipolar illness has been purported to be a possible trinucleotide repeat-associated disease. Since abnormalities in the expression and regulation of the sodium- and potassium-activated adenosine triphosphatase (Na,K-ATPase) have been documented in bipolar patients and since the β1 subunit of this pump contains a heterogenous GCC repeat, we decided to investigate the possibility of a repeat expansion in β1 subunit of Na,K-ATPase in bipolar patients. Methods: DNA from postmortem temporal cerebral cortex tissue of five bipolar subjects and five matched normal controls and five lyumphoblastoid cells lines from the Old Order Amish bipolar pedigrees and match normal controls were used for this study. The GCC rich region of β1 DNA was amplified by polymerase chain reaction (PCR) and sequenced. Results: The range of GCC repeat in the β1 gene is between 7 and 9 in our population. This is not different in bipolar patients from normal controls. Limitations: This study examined a small number of patients and examined a very limited portion of the locus. Conclusion: It appears that there is not an expansion of the GCC repeat in the β1 gene in bipolar patients.