Evidence for an allelic association between bipolar disorder and a Na+, K+ adenosine triphosphatase alpha subunit gene (ATP1A3)

Background: Disturbances in central nervous system Na+, K+ adenosine triphosphatase (ATPase) activity have previously been proposed as being involved in the pathophysiology of bipolar mood disorder. Methods: We have examined one particular alpha subunit of this enzyme for allelic association in a sample of 85 Irish bipolar patients and 85 matched controls. Results: There was evidence for an overall allelic association between the disease and a dinucleotide polymorphism within the ATP1A3 gene (p = .022). Subjects were then analyzed on the basis of a number of criteria, and the significance of the association increased when cases were divided based on the nature of the first episode. Patients who presented with a depressive episode first showed a significant association (p = .001) with this polymorphism. Conclusions: The results presented here provide preliminary evidence of an association between bipolar disorder and an alpha subunit of Na+, K+ ATPase, the expression of which predominates in the brain.