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Genetic analysis of interferon induced thyroiditis (IIT): evidence for a key role for MHC and apoptosis related genes and pathways.

ABSTRACT: Autoimmune thyroid diseases (AITD) have become increasingly recognized as a complication of interferon-alpha (IFN?) therapy in patients with chronic Hepatitis C virus (HCV) infection. Interferon-induced thyroiditis (IIT) can manifest as clinical thyroiditis in approximately 15% of HCV patients receiving IFN? and subclinical thyroiditis in up to 40% of patients, possibly resulting in either dose reduction or discontinuation of IFN? treatment. However, the exact mechanisms that lead to the development of IIT are unknown and may include IFN?-mediated immune-recruitment as well as direct toxic effects on thyroid follicular cells. We hypothesized that IIT develops in genetically predisposed individuals whose threshold for developing thyroiditis is lowered by IFN?. Therefore, our aim was to identify the susceptibility genes for IIT. We used a genomic convergence approach combining genetic association data with transcriptome analysis of genes upregulated by IFN?. Integrating results of genetic association, transcriptome data, pathway, and haplotype analyses enabled the identification of 3 putative loci, SP100/110/140 (2q37.1), HLA (6p21.3), and TAP1 (6p21.3) that may be involved in the pathogenesis of IIT. Immune-regulation and apoptosis emerged as the predominant mechanisms underlying the etiology of IIT.

SUBMITTER: Hasham A

PROVIDER: S-EPMC3740053 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Genetic analysis of interferon induced thyroiditis (IIT): evidence for a key role for MHC and apoptosis related genes and pathways.

Hasham Alia A Zhang Weijia W Lotay Vaneet V Haggerty Shannon S Stefan Mihaela M Concepcion Erlinda E Dieterich Douglas T DT Tomer Yaron Y

Journal of autoimmunity 20130515

Autoimmune thyroid diseases (AITD) have become increasingly recognized as a complication of interferon-alpha (IFNα) therapy in patients with chronic Hepatitis C virus (HCV) infection. Interferon-induced thyroiditis (IIT) can manifest as clinical thyroiditis in approximately 15% of HCV patients receiving IFNα and subclinical thyroiditis in up to 40% of patients, possibly resulting in either dose reduction or discontinuation of IFNα treatment. However, the exact mechanisms that lead to the develop ...[more]

PMID: 23683877

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Project description:Endometrial cancer (EC) is the fourth most common cancer in women worldwide. Although researchers are exploring the biological processes of tumorigenesis and development of EC, the gene interactions and biological pathways of EC are not accurately verified. In the present study, bioinformatics methods were used to screen for key candidate genes and pathways that were associated with EC and to reveal the possible mechanisms at molecular level. Microarray datasets (GSE63678, GSE17025 and GSE3013) from the Gene Expression Omnibus database were downloaded and 118 differentially expressed genes (DEGs) were selected using a Venn diagram. Functional enrichment analyses were performed on the DEGs. A protein-protein interaction network was constructed, including the module analysis. A total of 11 hub genes were identified from the DEGs, and functional enrichment analyses were performed to clarify their possible biological processes. A total of 118 DEGs were selected from three mRNA datasets. Functional enrichment demonstrated 27 downregulated genes that were primarily involved in the positive regulation of transcription from RNA polymerase II promoter, protein binding and the nucleus. A total of 91 upregulated DEGs were mainly associated with cell division, protein binding and the nucleus. Pathway analysis indicated that the downregulated DEGs were mainly enriched in pathways associated with cancer, and the upregulated DEGs were mainly enriched in the cell cycle. The 11 hub genes were primarily enriched in the cell cycle, oocyte meiosis, progesterone-mediated oocyte maturation, the p53 signaling pathway and viral carcinogenesis. The integrated analysis showed that cyclin B1, ubiquitin conjugating enzyme E2 C and cell division cycle 20 may participate in the tumorigenesis, development and invasion of EC. In conclusion, the hub genes and pathways identified in the present study contributed to the understanding of carcinogenesis and progression of EC at the mechanistic and molecular-biological level. As candidate targets for the diagnosis and treatment of EC, these genes deserve further investigation.

Dataset Information

Genetic analysis of interferon induced thyroiditis (IIT): evidence for a key role for MHC and apoptosis related genes and pathways.

Publications

Genetic analysis of interferon induced thyroiditis (IIT): evidence for a key role for MHC and apoptosis related genes and pathways.

Similar Datasets

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