Dataset Information

Prostate Cancer Related JAZF1 Gene is Associated with Schizophrenia.

ABSTRACT: BACKGROUND:Epidemiological studies have shown that there is a reduced risk of prostate cancer among persons diagnosed with schizophrenia (SCZ). However, the mechanism of such relationship is not clear. The reduced incidence of cancer observed in SCZ patients may be related to differences in genetic background. Recently, the JAZF1 gene is found to be associated with prostate cancer and type 2 diabetes. However, no study has focused on the association of JAZF1 with the risk of SCZ. METHODS:We examined genetic associations of 118 single-nucleotide polymorphisms (SNPs) within the JAZF1 gene with SCZ using one European American (EA) sample of 1,149 cases and 1,347 controls. Logistic regression analysis of SCZ as a binary trait was performed using PLINK software. RESULTS:The most significant association with SCZ was observed with rs10258132 (p = 0.0011); while the next best signal was rs17156259 (p = 0.0031). The third best associated SNP was rs7791865 (p = 0.00889). In addition, haplotype analyses revealed that the A-C haplotype from rs10244184 and rs10258132 was associated with SCZ (p = 0.00093); and the G-G haplotype from rs17156238 and rs17156259 was associated with SCZ (p = 0.00455). CONCLUSION:These findings provide evidence of several genetic variants in JAZF1 gene influencing the risk of SCZ and will serve as a resource for replication in other populations.

SUBMITTER: Wang KS

PROVIDER: S-EPMC4996122 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Prostate Cancer Related JAZF1 Gene is Associated with Schizophrenia.

Wang Ke-Sheng KS Zuo Lingjun L Owusu Daniel D Pan Yue Y Luo Xingguang X

Journal of schizophrenia research 20140801 1

<h4>Background</h4>Epidemiological studies have shown that there is a reduced risk of prostate cancer among persons diagnosed with schizophrenia (SCZ). However, the mechanism of such relationship is not clear. The reduced incidence of cancer observed in SCZ patients may be related to differences in genetic background. Recently, the JAZF1 gene is found to be associated with prostate cancer and type 2 diabetes. However, no study has focused on the association of JAZF1 with the risk of SCZ.<h4>Meth ...[more]

PMID: 27570842

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Project description:Prostate cancer is still the main male health problem in the world. The role of metabolism in the occurrence and development of prostate cancer is becoming more and more obvious, but it is not clear. Here we firstly identified a metabolism-related gene-based subgroup in prostate cancer. We used metabolism-related genes to divide prostate cancer patients from The Cancer Genome Atlas into different clinical benefit populations, which was verified in the International Cancer Genome Consortium. After that, we analyzed the metabolic and immunological mechanisms of clinical beneficiaries from the aspects of functional analysis of differentially expressed genes, gene set variation analysis, tumor purity, tumor microenvironment, copy number variations, single-nucleotide polymorphism, and tumor-specific neoantigens. We identified 56 significant genes for non-negative matrix factorization after survival-related univariate regression analysis and identified three subgroups. Patients in subgroup 2 had better overall survival, disease-free interval, progression-free interval, and disease-specific survival. Functional analysis indicated that differentially expressed genes in subgroup 2 were enriched in the xenobiotic metabolic process and regulation of cell development. Moreover, the metabolism and tumor purity of subgroup 2 were higher than those of subgroup 1 and subgroup 3, whereas the composition of immune cells of subgroup 2 was lower than that of subgroup 1 and subgroup 3. The expression of major immune genes, such as CCL2, CD274, CD276, CD4, CTLA4, CXCR4, IL1A, IL6, LAG3, TGFB1, TNFRSF4, TNFRSF9, and PDCD1LG2, in subgroup 2 was almost significantly lower than that in subgroup 1 and subgroup 3, which is consistent with the results of tumor purity analysis. Finally, we identified that subgroup 2 had lower copy number variations, single-nucleotide polymorphism, and neoantigen mutation. Our systematic study established a metabolism-related gene-based subgroup to predict outcomes of prostate cancer patients, which may contribute to individual prevention and treatment.

Project description:The objective of Human Y Chromosome Proteome Project is to map and annotate all proteins encoded by genes on the MSY sequences. Lysine (K)-specific demethylase 5D (KDM5D) is located on the AZFb region of Y chromosome and encode for a JmjC-domain-containing protein. Changes in KDM5D transcript level in prostate cancer have shown in various studies. To investigation the function of KDM5D in prostate cancer, we knocked down the expression of KDM5D in human prostate cancer cell (DU-145) using siRNA approach. Down-regulation of KDM5D was confirmed by qRT-PCR and western-blot analyses. Cell cycle analysis and MTS assay revealed that down-regulation of KDM5D induces cell proliferation. Furthermore, we observed that KDM5D down-regulation could effectively decrease apoptosis, as measured by the propidium iodide flow cytometric assay. To further our study, we investigated the dynamic of KDM5D protein network using shotgun label free quantitative proteomics approach in knockdown and control cell line. In summary, 102 down-regulated and 107 up-regulated proteins were detected from 894 total proteins. Up-regulated proteins mainly activated ribosome biogenesis whereas down-regulated genes were mainly involved in proteolysis, cell death and metabolic process. The result raw files were converted to mzXML format and processed through the global proteome machine (GPM) software (version 2.1.1) of the X!Tandem algorithm (freely available at http://www.thegpm.org). The 16 gel fractions were processed serially for each experiment and the output files were generated as non-redundant, merged files with protein identifications with log (e) values less than -1, for each individual gel fraction. A protein database compiled from NCBI (Homo sapien) was used in GPM to search the tandem mass spectra; the database also included common trypsin and human peptide contaminants. False discovery rates (FDR) were evaluated by searching against a reversed sequence database. Search parameters included MS and MS/MS tolerances of +2 Da and +0.2 Da, carbamidomethylation of cysteine as fixed modifications, oxidation of methionine as variable modifications and tolerance of two missed tryptic cleavages and K/R-P cleavages.

Dataset Information

Prostate Cancer Related JAZF1 Gene is Associated with Schizophrenia.

Publications

Prostate Cancer Related JAZF1 Gene is Associated with Schizophrenia.

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