IL28B基因多态性与聚乙二醇干扰素联合利巴韦林治疗波兰丙型肝炎病毒1型和4型感染患者疗效的相关性
Association of IL28B Polymorphisms With the Response to Peginterferon Plus Ribavirin Combined Therapy in Polish Patients Infected With HCV Genotype 1 and 4.
作者信息
Domagalski Krzysztof, Pawlowska Magorzata, Tretyn Andrzej, Halota Waldemar, Tyczyno Magorzata, Kozielewicz Dorota, Dybowska Dorota
机构信息
Department of Infectious Diseases and Hepatology, Nicolaus Copernicus University, Bydgoszcz, Poland ; Department of Plant Physiology and Biotechnology, Nicolaus Copernicus University, Torun, Poland.
Department of Infectious Diseases and Hepatology, Nicolaus Copernicus University, Bydgoszcz, Poland.
出版信息
Hepat Mon. 2013 Nov 25;13(11):e13678. doi: 10.5812/hepatmon.13678. eCollection 2013.
BACKGROUND
Three single nucleotide polymorphisms (SNPs) near interleukin-28B (IL-28B) gene were shown to be highly associated with treatment response (SVR) in patients with chronic hepatitis C virus (HCV) infection. There is limited data about the role of single and combined IL-28B polymorphisms in HCV-infected Polish population.
OBJECTIVES
This study's aim was to determine predictability of three IL-28B gene polymorphisms and other known prognostic factors on the treatment response in HCV genotype 1 and 4 infected Polish patients. The effect of IL-28B polymorphisms on therapy was also compared with other known prognostic factors.
PATIENTS AND METHODS
We genotyped IL-28B polymorphisms (rs12979860, rs12980275 and rs8099917) by polymerase chain reaction-based restriction fragment length polymorphism assay in a group of 293 patients from which a selected cohort of 174 treatment-naiev patients underwent treatment.
RESULTS
We showed that rs12979860 CC [odds ratio (OR) = 4.6, P < 0.001], rs12980275 AA (OR = 2.9, P = 0.002) and rs8099917 TT (OR = 2.2, P = 0.016) genotypes were associated with successful treatment compared to the rs12979860 CT-TT, rs12980275 AG-GG and rs8099917 TG-GG, respectively. Patients bearing of IL-28B profile including the three favourable genotypes do not have much chance of a recovery (OR = 3.4, P = 0.002). Except for IL-28B polymorphisms, there was no association of SVR with any other pretreatment clinical data in analyzed group. The correlation of SNPs with other host and viral factors revealed association of favorable genotypes of IL-28B markers with high levels of alanine aminotransferase and baseline HCV viral load.
CONCLUSIONS
IL-28B polymorphisms were the strongest pretreatment predictors of response to pegylated interferon and ribavirin in Polish patients chronically infected with HCV genotype 1 and 4. This study confirm the strongest impact of IL-28B rs12979860 on SVR, nevertheless rs12980275 AA seems to be more important than rs8099917 TT in predicting positive treatment response.
背景
白细胞介素-28B（IL-28B）基因附近的三个单核苷酸多态性（SNP）被证明与慢性丙型肝炎病毒（HCV）感染患者的治疗反应（持续病毒学应答，SVR）高度相关。关于单个及联合的IL-28B多态性在波兰HCV感染人群中的作用的数据有限。
目的
本研究旨在确定三个IL-28B基因多态性及其他已知预后因素对波兰HCV 1型和4型感染患者治疗反应的预测性。还将IL-28B多态性对治疗的影响与其他已知预后因素进行了比较。
患者与方法
我们采用基于聚合酶链反应的限制性片段长度多态性分析对293例患者的IL-28B多态性（rs12979860、rs12980275和rs8099917）进行基因分型，其中174例初治患者组成的选定队列接受了治疗。
结果
我们发现，与rs12979860 CT-TT、rs12980275 AG-GG和rs8099917 TG-GG相比，rs12979860 CC基因型（优势比[OR]=4.6，P<0.001）、rs12980275 AA基因型（OR=2.9，P=0.002）和rs8099917 TT基因型（OR=2.2，P=0.016）与治疗成功相关。具有包括这三种有利基因型的IL-28B谱型的患者康复机会不大（OR=3.4，P=0.002）。在分析的组中，除IL-28B多态性外，SVR与任何其他治疗前临床数据均无关联。SNP与其他宿主和病毒因素的相关性显示，IL-28B标记的有利基因型与高水平的丙氨酸转氨酶和基线HCV病毒载量相关。
结论
IL-28B多态性是波兰慢性感染HCV 1型和4型患者对聚乙二醇干扰素和利巴韦林治疗反应最强的治疗前预测指标。本研究证实IL-28B rs12979860对SVR的影响最大，不过在预测阳性治疗反应方面，rs12980275 AA似乎比rs8099917 TT更重要。
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