2014
DOI: 10.1002/jcp.24581
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Proteasome Modulator 9 Gene SNPs, Responsible for Anti‐Depressant Response, Are in Linkage With Generalized Anxiety Disorder

Abstract: Proteasome modulator 9 (PSMD9) gene single nucleotide polymorphism (SNP) rs1043307/rs2514259 (E197G) is associated with significant clinical response to the anti-depressant desipramine. PSMD9 SNP rs74421874 [intervening sequence (IVS) 3 + nt460 G>A], rs3825172 (IVS3 + nt437 C>T) and rs1043307/rs2514259 (E197G A>G) are all linked to type 2 diabetes (T2D), maturity-onset-diabetes-of the young 3 (MODY3), obesity and waist circumference, hypertension, hypercholesterolemia, T2D-macrovascular and T2D-microvascular d… Show more

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Cited by 19 publications
(15 citation statements)
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References 43 publications
(36 reference statements)
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“…We highlighted the possible gene pathways and mechanisms related to the neuro‐endocrine cortisol pathway impairment contributing to the clinical association of MDD and T2D (Gragnoli, , ). As previously mentioned, we also reported PSMD9 in linkage with T2D (Gragnoli, ), depression (Gragnoli, ), and the depression‐associated mental traits of generalized anxiety disorder (Gragnoli, ), and insomnia (Hao et al, ). PSMD9 is a highly concentrated ubiquitous PDZ‐domain‐containing chaperone of the 26S proteasome complex assembly and is an insulin gene transcription coactivator highly transcribed in pancreatic islets (Thomas, Yao, Tenser, Wong, & Habener, ).…”
Section: Mental and Metabolic Comorbiditysupporting
confidence: 68%
See 1 more Smart Citation
“…We highlighted the possible gene pathways and mechanisms related to the neuro‐endocrine cortisol pathway impairment contributing to the clinical association of MDD and T2D (Gragnoli, , ). As previously mentioned, we also reported PSMD9 in linkage with T2D (Gragnoli, ), depression (Gragnoli, ), and the depression‐associated mental traits of generalized anxiety disorder (Gragnoli, ), and insomnia (Hao et al, ). PSMD9 is a highly concentrated ubiquitous PDZ‐domain‐containing chaperone of the 26S proteasome complex assembly and is an insulin gene transcription coactivator highly transcribed in pancreatic islets (Thomas, Yao, Tenser, Wong, & Habener, ).…”
Section: Mental and Metabolic Comorbiditysupporting
confidence: 68%
“…Thus, at least one or a few genes and/or gene variants across this locus are expected to explain the pleiotropic or comorbid possibly unitarian linkage of the above‐mentioned phenotypes. One of these genes may be the PSMD9 gene as previously reported by us to be in linkage with several of the 12q24 linked phenotypes (T2D, depression, anxiety, hypertension, microvascular disease, retinopathy, hypercholesterolemia, overweight condition, and macrovascular disease) (Gragnoli, , , , , , , , , ; Gragnoli & Cronsell, ; Hao, Haas, Wu, & Gragnoli, ), and insomnia. Of note, PSMD9 has been reported by other groups as one of the top risk genes for MDD (Wong et al, , ) and SCZ (Lee et al, ).…”
Section: Mental and Metabolic Comorbiditymentioning
confidence: 91%
“…In this regard, it has been shown that single-nucleotide polymorphisms in proteasome subunit α7 (PSMA7), proteasome 26 S non-ATPase subunit 9 (PSMD9) and proteasome 26 S non-ATPase subunit 13 (PSMD13) are associated with the clinical antidepressant response. 79, 80 We therefore submit that UPS proteins such as PSMA2 and ubiquitination are of interest for evaluating and predicting clinical antidepressant treatment response.…”
Section: Discussionmentioning
confidence: 99%
“…Within the 12q24 locus 11 lies the gene of Proteasome-Modulator 9 ( PSMD9) , contributing to T2D through rare variants [rs149556654 SNP ( N166S A>G ) and S143G A>G variant] 12 . PSMD9 is significantly linked via the common single nucleotide polymorphisms (SNPs) rs74421874 ( IVS3+nt460 G>A ), rs3825172 ( IVS3+nt437 C>T ) and rs14259 ( E197G A>G ) to T2D 13 ; MODY3 14 ; T2D-neuropathy, T2D-nephropathy, T2D-retinopathy and non-diabetic retinopathy; T2D-microvascular 15 16 17 18 and T2D-macrovascular complications (stroke, coronary artery disease, myocardial infarction and vasculopathy) 19 ; carpal tunnel syndrome 20 ; hypercholesterolemia 21 ; overweight condition and waist circumference 22 ; hypertension 23 ; depression 24 , and anxiety 25 . Of note, the 12q24 locus is linked to T2D 11 ; macrovascular 26 27 , and microvascular disease 28 ; dyslipidemia 29 ; hypertension; obesity 30 , body mass index and C-reactive protein jointly 31 ; bipolar disorder 32 , depression 33 , and anxiety 34 .…”
mentioning
confidence: 99%