Genetic analysis of interferon induced thyroiditis (IIT): evidence for a key role for MHC and apoptosis related genes and pathways.
Genetic analysis of interferon induced thyroiditis (IIT): evidence for a key role for MHC and apoptosis related genes and pathways.
复制标题
干扰素诱导的甲状腺炎 (IIT) 的遗传分析：MHC 和细胞凋亡相关基因和途径发挥关键作用的证据。
DOI：
10.1016/j.jaut.2013.04.002
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发表时间：
2013
影响因子：
12.8
通讯作者：
Tomer,Yaron
中科院分区：
文献类型：
--
作者：
Hasham,Alia;Zhang,Weijia;Lotay,Vaneet;Haggerty,Shannon;Stefan,Mihaela;Concepcion,Erlinda;Dieterich,DouglasT;Tomer,Yaron
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 development of IIT are unknown and may include IFNα-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 IFNα. 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 IFNα. 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), andTAP1(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.
