Genetic variations in the PSMA3, PSMA6 and PSMC6 genes are associated with type 1 diabetes in Latvians and with expression level of number of UPS-related and T1DM-susceptible genes in HapMap individuals

Sjakste, Tatjana; Paramonova, Natalia; Ošiņa, Kristīne; Dokane, Kristine; Sokolovska, Jeļizaveta; Sjakste, Nikolajs

doi:10.1007/s00438-015-1153-0

Cited by 19 publications

(15 citation statements)

References 39 publications

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“…It regulates inflammatory processes and plays an important role in pathogenesis of human diseases such as cardiovascular diseases, diabetes, neurological diseases and cancer [7–10]. …”

Section: Introductionmentioning

confidence: 99%

Association between functional variant of inflammatory system gene (PSMA6) and end-stage kidney disease

et al. 2016

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BackgroundThe proteasome system is involved in several disorders. The 5′ untranslated region of PSMA6 gene contains a single nucleotide polymorphism (SNP) −8 C/G, associated with diabetes, myocardial infarction and coronary artery disease.MethodsWe examined 584 patients with end-stage kidney disease (ESKD) and 430 controls. All were genotyped for −8 C/G SNP by polymerase chain reaction and restriction analysis.ResultsWe observed lower frequency of CG + GG genotypes in patients than in controls (20 vs. 42 %, p = 0.0038). The odds ratio of 0.34 (95 % CI 0.26–0.45) suggests association of CG + GG with decreased risk of ESKD. We investigated the association between PSMA6 polymorphism and LVH present in 54 % of patients. There was a significant association of CG + GG genotype with LVH, with over 75 % of CG + GG in patients with LVH. This effect was independent from other common causes of LVH—age (OR 1.12, p = 0.643) and hypertension (OR 1.72, p = 0.422).ConclusionWe demonstrated for the first time that PSMA6 polymorphism might be a protective factor for ESKD. On the other hand, CG + GG genotypes are independently related to LVH in ESKD patients.

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“…It regulates inflammatory processes and plays an important role in pathogenesis of human diseases such as cardiovascular diseases, diabetes, neurological diseases and cancer [7–10]. …”

Section: Introductionmentioning

confidence: 99%

Association between functional variant of inflammatory system gene (PSMA6) and end-stage kidney disease

et al. 2016

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“…On the other hand, ARL6IP1 and PSMC6 have been associated with insulin synthesis and pathology of diabetes, respectively 30,31 . Also, ARL6IP1 protein is associated phosphatidylethanolamine-binding family of proteins (PEBP1), which has important role in MAPK, NF-kappa B, and glycogen synthase kinase-3 (GSK-3) signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Altered pathways in methylome and transcriptome longitudinal analysis of normal weight and bariatric surgery women

Nicoletti

Pinhel

Noronha

et al. 2020

Sci Rep

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DnA methylation could provide a link between environmental, genetic factors and weight control and can modify gene expression pattern. This study aimed to identify genes, which are differentially expressed and methylated depending on adiposity state by evaluating normal weight women and obese women before and after bariatric surgery (BS). We enrolled 24 normal weight (BMI: 22.5 ± 1.6 kg/m 2 ) and 24 obese women (BMI: 43.3 ± 5.7 kg/m 2 ) submitted to BS. Genome-wide methylation analysis was conducted using Infinium Human Methylation 450 BeadChip (threshold for significant CpG sites based on delta methylation level with a minimum value of 5%, a false discovery rate correction (FDR) of q < 0.05 was applied). Expression levels were measured using HumanHT-12v4 Expression BeadChip (cutoff of p ≤ 0.05 and fold change ≥2.0 was used to detect differentially expressed probes). The integrative analysis of both array data identified four genes (i.e. TPP2, PSMG6, ARL6IP1 and FAM49B) with higher methylation and lower expression level in pre-surgery women compared to normal weight women: and two genes (i.e. ZFP36L1 and USP32) that were differentially methylated after BS. These methylation changes were in promoter region and gene body. All genes are related to MAPK cascade, NIK/NF-kappaB signaling, cellular response to insulin stimulus, proteolysis and others. integrating analysis of DnA methylation and gene expression evidenced that there is a set of genes relevant to obesity that changed after BS. A gene ontology analysis showed that these genes were enriched in biological functions related to adipogenesis, orexigenic, oxidative stress and insulin metabolism pathways. Also, our results suggest that although methylation plays a role in gene silencing, the majority of effects were not correlated.DNA methylation in CpG dinucleotides is a dynamic process and best characterized epigenetic modifications 1 . Methylation patterns are established in early life and can be remodeled in adult cells, by modulating DNA interactions with proteins and transcription factors 2,3 , being able to alter gene expression profile 4 .Weight gain or loss during infancy and adulthood, by changing the energy storage and adipose tissue homeostasis, may alter molecular mechanisms and biological processes 5 . In line of this, epigenetic changes may predispose a disease risk or can occur once a disease has developed 6 . Thus, DNA methylation provides a link between environmental, genetic factors and weight control.Obesity has reached epidemic proportions and, in 2016, affected about 1.9 billion adults worldwide 7 , being associated to a public health burden. In the context of obesity treatment, bariatric surgery (BS) has been the best choice for cases of severe obesity and has been shown to be the most effective way to promote significant and sustained weight loss 8 . Among the surgical techniques, Roux-en-Y gastric bypass (RYGB) is the most performed in Brazil and worldwide, and is considered a gold standard because its high efficacy and low morbid-mortalit...

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“…DUSP9 was involved in progression of cardiac hypertrophy [58], but this gene may be responsible for progression of CAD. Mutation in PSMC6 was important for progression of type 1 diabetes [59], but variation in this gene may be associated with the development of CAD. Decrease expression of ATP5H was liable for progression of mitochondrial dysfunction in cardiomyocytes [60], but low expression of this gene may be linked with the advancement of CAD.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Differentially Expressed Genes in Coronary Artery Disease by Integrated Microarray Analysis

et al. 2019

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Coronary artery disease (CAD) is a major cause of end-stage cardiac disease. Although profound efforts have been made to illuminate the pathogenesis, the molecular mechanisms of CAD remain to be analyzed. To identify the candidate genes in the advancement of CAD, microarray dataset GSE23766 was downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified, and pathway and gene ontology (GO) enrichment analyses were performed. The protein-protein interaction network was constructed and the module analysis was performed using the Biological General Repository for Interaction Datasets (BioGRID) and Cytoscape. Additionally, target genes-miRNA regulatory network and target genes-TF regulatory network were constructed and analyzed. There were 894 DEGs between male human CAD samples and female human CAD samples, including 456 up regulated genes and 438 down regulated genes. Pathway enrichment analyses revealed that DEGs (up and down regulated) were mostly enriched in the superpathway of steroid hormone biosynthesis, ABC transporters, oxidative ethanol degradation III and Complement and coagulation cascades. Similarly, geneontology enrichment analyses revealed that DEGs (up and down regulated) were mostly enriched in the forebrain neuron differentiation, filopodium membrane, platelet degranulation and blood microparticle. In the PPI network and modules (up and down regulated), MYC, NPM1, TRPC7, UBC, FN1, HEMK1, IFT74 and VHL were hub genes. In the target genes-miRNA regulatory network and target genes—TF regulatory network (up and down regulated), TAOK1, KHSRP, HSD17B11 and PAH were target genes. In conclusion, the pathway and GO ontology enriched by DEGs may reveal the molecular mechanism of CAD. Its hub and target genes, MYC, NPM1, TRPC7, UBC, FN1, HEMK1, IFT74, VHL, TAOK1, KHSRP, HSD17B11 and PAH were expected to be new targets for CAD. Our finding provided clues for exploring molecular mechanism and developing new prognostics, diagnostic and therapeutic strategies for CAD.

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Genetic variations in the PSMA3, PSMA6 and PSMC6 genes are associated with type 1 diabetes in Latvians and with expression level of number of UPS-related and T1DM-susceptible genes in HapMap individuals

Cited by 19 publications

References 39 publications

Association between functional variant of inflammatory system gene (PSMA6) and end-stage kidney disease

Association between functional variant of inflammatory system gene (PSMA6) and end-stage kidney disease

Altered pathways in methylome and transcriptome longitudinal analysis of normal weight and bariatric surgery women

Analysis of Differentially Expressed Genes in Coronary Artery Disease by Integrated Microarray Analysis

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