Chuang J Y, Yang S S, Lu Y T, Hsieh Y Y, Chen C Y, Chang S C, Chang C S, Yeh H Z, Kao J H
Graduate Institute and Department of Medical Laboratory Science and Biotechnology, College of Health Care, China Medical University, Taichung, Taiwan.
Dig Liver Dis. 2009 Jun;41(6):424-30. doi: 10.1016/j.dld.2008.09.017. Epub 2008 Nov 11.
Host genetic factors may affect clinical outcomes of hepatitis C virus (HCV) infection; however, the possible mechanisms remain largely unknown. The role of immunopathogenesis in chronic hepatitis C leads to extensive exploration of host immunity including inflammatory cytokines.
We examined interleukin 10 (IL-10) promoter gene polymorphisms at positions -1082, -819, and -592 relative to transcription start site and studied their association with response to 24 weeks of pegylated interferon plus ribavirin treatment in 143 chronic hepatitis C patients, of whom 97 (67.8%) achieved a sustained virologic response (SVR). In addition, 134 healthy adults were used as controls.
Of chronic hepatitis C patients, 111 (77.6%) were genotype 1 infection, 32 (22.4%) were genotype 2 infection. Patients with sustained virologic response were younger and had higher pretreatment ALT levels than those without. No statistical difference was found between chronic hepatitis C patients who achieved SVR or not in terms of gender, HCV genotype, pretreatment HCV RNA levels, and severity of liver disease. The serum IL-10 levels were comparable between healthy controls and chronic hepatitis C patients as well as between HCV patients with and without SVR. The distribution of IL-10 promoter gene polymorphisms at positions -1082, -819, and -592 relative to transcription start site was comparable between HCV patients and healthy controls as well as HCV patients with and without SVR. A high frequency of ATA haplotype of common IL-10 promoter gene SNPs was found in both chronic hepatitis C patients (70.3%) and healthy controls (69.8%). However, ATA haplotype was not associated with SVR in chronic hepatitis C patients.
Our data fail to demonstrate the influence of IL-10 promoter gene polymorphisms on the response to combination therapy in Taiwanese chronic hepatitis C patients. The impact of genetic variations in IL-10 haplotype on the response to anti-HCV treatment among different ethnic populations deserves further examination.
宿主遗传因素可能影响丙型肝炎病毒（HCV）感染的临床结局；然而，其潜在机制仍大多未知。免疫发病机制在慢性丙型肝炎中的作用促使人们对包括炎性细胞因子在内的宿主免疫进行广泛探索。
我们检测了相对于转录起始位点在-1082、-819和-592位置的白细胞介素10（IL-10）启动子基因多态性，并研究了它们与143例慢性丙型肝炎患者接受聚乙二醇干扰素联合利巴韦林治疗24周的反应之间的关联，其中97例（67.8%）实现了持续病毒学应答（SVR）。此外，134名健康成年人作为对照。
在慢性丙型肝炎患者中，111例（77.6%）为1型感染，32例（22.4%）为2型感染。实现持续病毒学应答的患者比未实现的患者更年轻且治疗前ALT水平更高。在实现SVR的慢性丙型肝炎患者与未实现SVR的患者之间，在性别、HCV基因型、治疗前HCV RNA水平和肝病严重程度方面未发现统计学差异。健康对照与慢性丙型肝炎患者之间以及有和没有SVR的HCV患者之间血清IL-10水平相当。相对于转录起始位点在-1082、-819和-592位置的IL-10启动子基因多态性分布在HCV患者与健康对照之间以及有和没有SVR的HCV患者之间相当。在慢性丙型肝炎患者（70.3%）和健康对照（69.8%）中均发现常见IL-10启动子基因单核苷酸多态性的ATA单倍型频率较高。然而，ATA单倍型与慢性丙型肝炎患者的SVR无关。
我们的数据未能证明IL-10启动子基因多态性对台湾慢性丙型肝炎患者联合治疗反应的影响。IL-10单倍型基因变异对不同种族人群抗HCV治疗反应的影响值得进一步研究。
