Proteasome Modulator 9 and Depression in Type 2 Diabetes

Background: The chromosome 12q24 locus is linked to bipolar disorder, depression, and type 2 diabetes (T2D). PSMD9 lies in the 12q24 locus and is linked to MODY3, T2D, T2D-nephropathy, T2D-neuropathy, retinopathy, macrovascular pathology, hypertension, and hypercholesterolemia in Italian families. Interestingly, PSMD9 gene common variants contribute to the therapeutic response to anti-depressant treatment. Further, PSMD9 is implicated in a model of prediction to susceptibility to depression. Aims: Our goal was to determine whether PSMD9 is linked to depression in 200 T2D Italian families. Methods: We characterized the Italian families' members for presence and/or absence of depression using the diagnostic criteria of DSM-IV. The phenotype was described as unknown in all cases in which the diagnosis was unclear or data were not available. We tested in the 200 Italians families for evidence of linkage of the PSMD9 single nucleotide polymorphisms (SNPs) IVS3+nt460 A>G, IVS3+nt437 T>C and E197G A>G with the depression phenotype. The non-parametric linkage analysis was performed by using the Merlin software. To rule out results due to random chance, 1000 replicates were executed. Results: The PSMD9 gene SNPs studied and/or any gene variants in linkage disequilibrium with them are linked to depression in our Italian families. Conclusions: This is the first report of PSMD9 linkage to depression. This finding highlights the pleiotropic effects of PSMD9.