What is the role of the ANK3 (ankyrin G) and CACNA1C (alpha 1C subunit of the L-type voltage-gated calcium channel) genes in the pathogenesis of bipolar affective disorder (manic-depressive illness)?

Updated: May 06, 2018
  • Author: Stephen Soreff, MD; Chief Editor: Glen L Xiong, MD  more...
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Answer

The first series of genome-wide association studies (GWASs) for bipolar disorder were published in 2007 and 2008, [18, 19, 20, 16] and a collaborative analysis of the last 3 studies gave combined support for 2 particular genes, ANK3 (ankyrin G) and CACNA1C (alpha 1C subunit of the L-type voltage-gated calcium channel) in a sample of 4387 cases and 6209 controls. [16] ANK3 is an adaptor protein found at axon initial segments that regulates the assembly of voltage-gated sodium channels. Both ANK3 and subunits of the calcium channel are downregulated in mouse brain in response to lithium, which indicates a possible therapeutic mechanism of action of one of the most effective treatments for bipolar disorder. [21]

Further evidence for association of bipolar disorder to CACNA1C was reported in 2011 in an ever-growing sample (numbering 11,974 bipolar disorder cases and 51,792 controls at the time of the report), providing overwhelming support for this gene as a bipolar susceptibility locus. [17]


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