IL-10促動基因多型性對慢性C型肝炎患者的疾病嚴重度與治療療效之影響

Association between IL-10 gene promoter polymorphisms and severity of disease and response to therapy for chronic hepatitis C patients

丘筠瑄(Yun-Shiuan Chiou)

指導教授 ： 林信仁

共同指導教授 ： 余明隆

高雄醫學大學/生命科學院/醫藥暨應用化學研究所碩士在職專班/碩士(2006年)

https://doi.org/10.6832/KMU.2006.00123

摘要

C型肝炎病毒是1989年被發現，它不是直接造成細胞的病變，而是藉由不斷地觸動免疫反應導致發炎進而持續地損害肝臟。所以研究可能影響免疫反應的因子例如細胞激素與C型肝炎的關係對於病患的影響或許可找出另一個治療C型肝炎的思考方向。近年來另一種抗病毒藥物ribavirin被發現和干擾素合併使用可以明顯提高其療效至40-50%左右。少許研究發現ribavirin可以降低IL-10之分泌，進而促進IFN-α對慢性C型肝炎之療效。這些研究結果顯示IL-10在合併ribavirin與甲型干擾素對提升慢性C型肝炎治療療效可能扮演重要的角色。根據相關研究顯示，IL-10濃度與IL-10促動基因多型性有關，尤其是在-1082、-819、及-592三點之多型性變化與IL-10基因表現更有相關。所以針對IL-10促動基因變異性在慢性C型肝炎患者之研究，將有助於從免疫遺傳學瞭解宿主免疫系統與C型肝炎病毒感染之病程發展。我們的研究結果顯示在212位慢性C型肝炎病患當中具-1082G包括-1082G/A基因型或GCC/ACC、GCC/ATA之患者明顯有較高之肝硬化比率，顯示IL-10促動基因多型性與慢性C型肝炎病患肝硬化有關 (P<0.05, OR=4.55)。但IL-10三個核苷酸多型性之分佈則與病人肝臟組織病理發炎程度及血中病毒濃度無關。其他相關因子例如性別、年齡、病毒濃度、基因型與IL-10促動基因多型性皆無相關性。針對IL-10促動基因多型性對治療慢性C型肝炎患者的療效影響方面，顯示在治療療效方面，還是以病毒量、基因型、肝臟發炎指數較具相關性，而IL-10促動基因多型性在我們的研究結果中並無發現其與治療療效有關。本研究結果顯示IL-10促動基因多型性可能與慢性C型肝炎致病之機轉有關，與其抗病毒治療療效無關。

關鍵字

C型肝炎 ； 促動基因多型性

並列摘要

The hepatitis C virus (HCV) was discovered in 1989. The pathogenesis of hepatitis C was attributed more to continuous inflammation caused by immune response induced by HCV rather than the direct cytopathic effect of HCV itself. Therefore the researches on the relationship between factors of the immune response, for example, the cytokines and the related genetic effect, and the clinical manifestation of chronic hepatitis C (CHC) are essential and critical to elucidating further therapy.
Ribavirin, an antiviral agent administered orally, was found recently to increase the rate of sustained virological response (SVR) to 40-50% of CHC therapy when combined with interferon-alpha (IFN-alpha). Several studies have reported that ribavirin reduced secretion of interleukin 10 (IL-10), a potent anti-inflammatory Th2 cytokine, and enhanced the therapeutic effects of IFN-alpha. Hence IL-10 might play a role in the pathogenesis and therapy of CHC with IFN/ribavirin combination therapy. According to previous studies, IL-10 levels differ widely between individuals possibly because of polymorphisms in the promoter region of the IL-10 gene. Specifically, 3 single nucleotide polymorphisms (SNPs) in the promoter region (at positions –1082, –819, and –592 relative to the transcription start site) were associated with differential IL-10 expression. Thus, studying the IL-10 gene promoter polymorphisms in the CHC patients will be helpful to elucidate the relationship between host immunity and characteristics of CHC from the immunogenetic point of view.In the present study enrolling 212 patients with chronic hepatitis C, we found that patients with the G allele at position -1082 had higher proportion of liver cirrhosis which indicated the association between G allele at position -1082 and liver cirrhosis. No correlation between IL-10 gene promoter haplotype and alanine aminotransferase levels. No correlation between age, gender, HCV viral load as well as HCV genotype and IL-10 gene promoter polymorphisms. For therapy of CHC with IFN alone or combined with ribavirin, the viral load, genotype and ALT level were factors related to the SVR. The IL-10 gene promoter polymorphisms were not associated with the response of therapy for CHC in the present study.

並列關鍵字

IL-10 ； polymorphisms

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