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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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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.

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