For example, disrupted in schizophrenia 1 (DISC1) normally regulates cAMP levels, while regulator of G protein signaling 4 (RGS4) and diacylglycerol kinase (DGKH)-the molecule most associated with bipolar disorder- normally serve to inhibit phosphatidylinositol-protein kinase C intracellular signaling.
Various other protein products of genes associated with bipolar disorder either bind to or are affected by phosphatidyl-inositol phosphate products of this pathway (ADBRK2, HIP1R, KCNQ2, RGS4, WFS1), are associated with its constituent elements (BCR, DUSP6, FAT, GNAZ) or are downstream targets of this signalling cascade (DPYSL2, DRD3, GAD1, G6PD, GCH1, KCNQ2, NOS3, SLC6A3, SLC6A4, SST, TH, TIMELESS).
Single-nucleotide polymorphisms (SNPs) were genotyped in the DTNBP1 (dysbindin), G72/G30 and RGS4 genes, and the relatively unknown PIP5K2A gene, which is located in a region of linkage with both schizophrenia and bipolar disorder.
In conclusion, we could not find evidence of association between RGS4, PRODH, COMT and GRK3 genes and bipolar affective disorder 1 in the Scottish population.