Dataset Information

Integrative genomic and transcriptomic analysis of genetic markers in Dupuytren's disease.

ABSTRACT:

Background

Dupuytren's disease (DD) is a fibroproliferative disorder characterized by thickening and contracting palmar fascia. The exact pathogenesis of DD remains unknown.

Results

In this study, we identified co-expressed gene set (DD signature) consisting of 753 genes via weighted gene co-expression network analysis. To confirm the robustness of DD signature, module enrichment analysis and meta-analysis were performed. Moreover, this signature effectively classified DD disease samples. The DD signature were significantly enriched in unfolded protein response (UPR) related to endoplasmic reticulum (ER) stress. Next, we conducted multiple-phenotype regression analysis to identify trans-regulatory hotspots regulating expression levels of DD signature using Genotype-Tissue Expression data. Finally, 10 trans-regulatory hotspots and 16 eGenes genes that are significantly associated with at least one cis-eQTL were identified.

Conclusions

Among these eGenes, major histocompatibility complex class II genes and ZFP57 zinc finger protein were closely related to ER stress and UPR, suggesting that these genetic markers might be potential therapeutic targets for DD.

SUBMITTER: Jung J

PROVIDER: S-EPMC6624179 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

Integrative genomic and transcriptomic analysis of genetic markers in Dupuytren's disease.

Jung Junghyun J Kim Go Woon GW Lee Byungjo B Joo Jong Wha J JWJ Jang Wonhee W

BMC medical genomics 20190711 Suppl 5

<h4>Background</h4>Dupuytren's disease (DD) is a fibroproliferative disorder characterized by thickening and contracting palmar fascia. The exact pathogenesis of DD remains unknown.<h4>Results</h4>In this study, we identified co-expressed gene set (DD signature) consisting of 753 genes via weighted gene co-expression network analysis. To confirm the robustness of DD signature, module enrichment analysis and meta-analysis were performed. Moreover, this signature effectively classified DD disease ...[more]

PMID: 31296227

Similar Datasets

Project description:PURPOSE: Dupuytren's disease (DD) is characterized by fibroblastic proliferation of the palmar fascia, often leading to flexion contracture in the hand. Although there is a strong genetic component the genome-wide expression of novel genes is not known. The purpose of this study was to use DNA microarray technology to identify upregulated genes in DD. METHODS: Human tissue samples were harvested from 3 patient sources: DD cord tissue (n = 20), normal-appearing adjacent control fascia (n = 15), and palmar fascia from patients having carpal tunnel release (n = 15). DNA microarray analysis was performed on amplified sample RNA. Novel genes were compared with known gene functions. A candidate gene of interest was studied further by using immunohistochemistry on DD tissue samples and controls. : Several novel genes not described previously in the study of DD were upregulated significantly, including MafB, collagen type V, alpha-2 (COL5A2), collagen type VIII, alpha-1 (COL8A1), contactin I (CNTN1), and leucine-rich repeat containing 17 (LRRC17). These upregulated genes were compared with their known gene-expression profiles in other tissues and their purported functions. MafB was found to be of particular interest because of its prominent role in tissue development and cellular differentiation. MafB immunohistochemistry showed positive staining in 50% of the DD specimens but complete absence of MafB in all control tissues (adjacent control fascia, carpal tunnel fascia). Co-localization experiments with MafB and alpha-smooth muscle actin showed staining properties in similar regions but these 2 proteins were not confined solely to the same cells. CONCLUSIONS: Microarray analysis of DD tissue has identified significant upregulated gene expression of MafB. MafB protein also is found in Dupuytren's cords but not in control fascia. Co-localization data suggest that the association of MafB with DD is not related exclusively to myofibroblast proliferation. Because of its role in fibroblastic transformation in other models MafB and its relationship to the pathogenesis of DD deserves further study. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Keywords: Logical Set

Dataset Information

Integrative genomic and transcriptomic analysis of genetic markers in Dupuytren's disease.

Background

Results

Conclusions

Publications

Integrative genomic and transcriptomic analysis of genetic markers in Dupuytren's disease.

Similar Datasets

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