T2D and Depression Risk Gene Proteasome Modulator 9 is Linked to Insomnia

Han, Hongjing; Haas, Michael J.; Wu, Rongling; Gragnoli, Claudia

doi:10.1038/srep12032

Cited by 9 publications

(8 citation statements)

References 55 publications

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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%

“…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%

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Co‐shared genetics and possible risk gene pathway partially explain the comorbidity of schizophrenia, major depressive disorder, type 2 diabetes, and metabolic syndrome

Postolache

Bosque-Plata

Jabbour

et al. 2019

American J of Med Genetics Pt B

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Schizophrenia (SCZ) and major depressive disorder (MDD) in treatment-naive patients are associated with increased risk for type 2 diabetes (T2D) and metabolic syndrome (MetS). SCZ, MDD, T2D, and MetS are often comorbid and their comorbidity increases cardiovascular risk: Some risk genes are likely co-shared by them. For instance, transcription factor 7-like 2 (TCF7L2) and proteasome 26S subunit, non-ATPase 9 (PSMD9) are two genes independently reported as contributing to T2D and SCZ, and PSMD9 to MDD as well. However, there are scarce data on the shared genetic risk among SCZ, MDD, T2D, and/or MetS. Here, we briefly describe T2D, MetS, SCZ, and MDD and their genetic architecture. Next, we report separately about the comorbidity of SCZ and MDD with T2D and MetS, and their respective genetic overlap. We propose a novel hypothesis that genes of the prolactin (PRL)-pathway may be implicated in the comorbidity of these disorders. The inherited predisposition of patients with SCZ and MDD to psychoneuroendocrine dysfunction may confer increased risk of T2D and MetS. We illustrate a strategy to identify risk variants in each disorder and in their comorbid psychoneuroendocrine and mentalmetabolic dysfunctions, advocating for studies of genetically homogeneous and phenotype-rich families. The results will guide future studies of the shared predisposition and molecular genetics of new homogeneous endophenotypes of SCZ, MDD, and metabolic impairment.

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Section: Mental and Metabolic Comorbiditysupporting

confidence: 68%

Section: Mental and Metabolic Comorbiditymentioning

confidence: 91%

Co‐shared genetics and possible risk gene pathway partially explain the comorbidity of schizophrenia, major depressive disorder, type 2 diabetes, and metabolic syndrome

Postolache

Bosque-Plata

Jabbour

et al. 2019

American J of Med Genetics Pt B

Self Cite

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“…PSMD9 is a transcriptional regulator of insulin gene transcription and variants can contribute to type 2 DM by causing beta-cell dysfunction; therefore, single nucleotide polymorphisms (SNP) of transcriptional regulators can alter the expression of neurotransmitters, and neuronal ion channels and their receptors, which can lead to DSPN and neuropathic pain ( 3 , 11 , 12 ). Earlier studies reported that PSMD9 rs14259 (E197G-A >G) polymorphism is associated with type 2 DM, depression, schizophrenia, anxiety, maturity-onset diabetes-of the young 3/MODY3, obesity, increased waist circumference, hypertension, hypercholesterolemia, type 2 DM-macrovascular diseases, type 2 DM-microvascular disease, type 2 DM-neuropathy, type 2 DM-carpal-tunnel syndrome, type 2 DM-nephropathy, type 2 DM-retinopathy, and non-diabetic retinopathy ( 13 – 17 ).…”

Section: Discussionmentioning

confidence: 99%

Proteasome modulator 9 gene rs14259 polymorphism in patients with diabetic polyneuropahy

Salcini¹,

Sünter²,

Arslan³

et al. 2020

Archives of Neuropsychiatry

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Introduction: Diabetic polyneuropathy (DPN) is a major chronic neurological complication of diabetes mellitus (DM) and typically presents as diabetic sensory polyneuropathy (DSPN). Whereas some patients with similar risk factors develop polyneuropathy, others don’t, which suggests that genetics plays an important role in the progression of disease. The proteasome modulator 9 gene (PSMD9) is a transcriptional regulator of the insulin gene and its variants cause beta-cell dysfunction that devastates insulin transcription. The aim of this study was to determine the correlation between PSMD9 rs14259 polymorphism and the risk of DSPN in Turkish DM patients with DPN. Methods: The study included 31 DM patients with DSPN and 29 healthy controls. All participants underwent electrophysiological investigation. In addition, DNA was isolated from peripheral blood samples for the genotyping of PSMD9 rs14259 polymorphism. Results: Mean age in the DSPN and control groups was 58.03±9.59 years and 57.62±12.32 years, respectively. There were significant differences between the DSPN and controls groups in the frequencies of the genotype for AA (n=9 and n=12, respectively), AG (n=10 and n=15, respectively), and GG (n=12 and n=2, respectively). According to the distribution of PSMD9 rs14259 polymorphism, 45.2% (n=28) of the patients and 67.2% (n=39) of the controls had the A allele, and 54.8% (n=34) of the patients and 32.8% (n=19) of the controls had the G allele, whereas the frequency of the G allele of rs14259 was significantly higher in the DSPN group (X 2 =1.059, P=0.015) than in the control group (OR: 2.49; 95% CI: 1.18–5.23). Conclusion: The present findings show that the GG genotype and G allele of PSMD9 rs14259 polymorphism may be associated with an increased risk of DSPN in Turkish DM patients.

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“…Proteasome modulator 9 (PSMD9) is a part of the 26S proteasome complex degrading intracellular proteins in the immune response and antigen presentation by MHC class I cells. It was demonstrated that PSMD9 inhibited tumor necrosis factor α (TNF-α)-mediated NF-kB activation via inhibition of nuclear factor kBα (IkBα) proteasome degradation (Hao et al, 2015). TNF-α is one determinant of AD and T2DM onset and progression (Tsutsui and Hays, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…TNF-α is one determinant of AD and T2DM onset and progression (Tsutsui and Hays, 2018). In addition, the proteasome-mediated proteolysis plays a recognized role in neuronal development, synaptic plasticity, and protein quality control (Hao et al, 2015). Thus, PSMD9 variants might play a role in neuroinfl ammation and many neurodegenerative diseases.…”

Section: Introductionmentioning

confidence: 99%

Proteasome modulator 9 (PSMD9) gene rs14259 polymorphism in Alzheimer’s disease

Ozer¹,

Ozen²,

Diler³

et al. 2020

BLL

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AIM: Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disorder resulting in degeneration of certain neuronal structures in certain brain regions and severe neuronal loss, characterized by a pathological accumulation of senile amyloid plaques (SP) and neurofi brillary tangles (NFT) within the brain . Alzheimer's disease has been associated with Type 2 diabetes mellitus (T2DM) in recent years. We designed our study on the relationship between AD and T2DM. Genome screening studies in different populations had linked the chromosome 12q24 region to type 2 diabetes. Within this region, there is the PSMD9 gene encoding a transcriptional coactivator of insulin production. METHOD: The effect of PSMD9 gene E197G (rs14259) polymorphism on AD was investigated in29 Alzheimer's patients and 25 healthy controls, who were included in the study. RESULTS: In our study, it was determined that the variant of PSMD9 gene E197G (rs14259) did not cause genetic risk factor for Alzheimer's disease in Turkish population. CONCLUSIONS: Our study was the fi rst to investigate the relationship between PSMD9 gene and Alzheimer's disease. A larger sample group is needed to investigate the contribution of the PSMD9 gene to Alzheimer's disease in further studies (Tab. 5, Ref. 8).

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T2D and Depression Risk Gene Proteasome Modulator 9 is Linked to Insomnia

Cited by 9 publications

References 55 publications

Co‐shared genetics and possible risk gene pathway partially explain the comorbidity of schizophrenia, major depressive disorder, type 2 diabetes, and metabolic syndrome

Co‐shared genetics and possible risk gene pathway partially explain the comorbidity of schizophrenia, major depressive disorder, type 2 diabetes, and metabolic syndrome

Proteasome modulator 9 gene rs14259 polymorphism in patients with diabetic polyneuropahy

Proteasome modulator 9 (PSMD9) gene rs14259 polymorphism in Alzheimer’s disease

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