El-Awady Mostafa K, Mostafa Lotiaf, Tabll Ashraf A, Abdelhafez Tawfeek H, Bader El Din Noha G, Zayed Naglaa, Shenawy Reem El, El Abd Yasmin, Hasan Reham M, Zaghlol Hosam, El Khayat Hesham, Abdel Aziz Ashraf O
Department of Microbial Biotechnology, National Research Center, Giza, Egypt.
Hepat Mon. 2012 Apr;12(4):271-7. doi: 10.5812/hepatmon.835. Epub 2012 Apr 30.
IL28B single nucleotide polymorphisms (SNPs) play important roles in the management of hepatitis C virus (HCV) infections and are strongly associated with spontaneous and treatment-induced HCV clearance.
In the present study, the association between IL28B variants and the progression of HCV infection in Egyptian patients infected with type 4a virus will be examined.
Frequencies of the protective genotype C/C of SNP, rs12979860 were determined in healthy subjects, spontaneous resolvers, and chronic HCV type 4 patients with low F scores and in patients with end stage liver disease (ESLD). This study included a total of 404 subjects. Patients infected with HCV type 4a (n = 304) were divided into; chronic hepatitis C (CHC) with low F scores (CHC, n = 110), end stage liver disease (n = 110), liver cirrhosis (LC) (n = 35) and hepatocellular carcinoma (HCC) patients (n = 75), spontaneous resolvers of HCV infection (n = 84) were also included. A healthy group representing the Egyptian population (n = 100) was also included in the genotyping of IL28B. The later was typed via a polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) assay analysis on purified genomic DNA extracted from all individuals.
A significant increase (P < 0.0005) was observed in frequencies of IL-28B rs12979860 C/C genotypes in the healthy population, than in the CHC, LC and HCC groups (C/C = 48%, 13%, 0%.and 0% respectively). On the other hand the C/C genotype was significantly higher (P < 0.0005) in spontaneous resolvers than in healthy subjects. A comparable significant increase in the frequency of C/T allele accompanied by mild elevation of T/T allele frequency, were detected along the progression towards ESLD.
Genotype C/C is associated with viral clearance during acute infection. The sharp decline in the C/C genotype from healthy to CHC subjects and the total absence of the C/C genotype in ESLD suggests a central role of this genotype against HCV disease progression.
白细胞介素28B单核苷酸多态性（SNPs）在丙型肝炎病毒（HCV）感染的管理中发挥重要作用，并且与HCV的自发清除和治疗诱导清除密切相关。
在本研究中，将检测白细胞介素28B基因变异与感染4a型病毒的埃及患者中HCV感染进展之间的关联。
在健康受试者、自发清除者、F评分低的慢性4型HCV患者以及终末期肝病（ESLD）患者中，测定单核苷酸多态性rs12979860的保护性基因型C/C的频率。本研究共纳入404名受试者。感染4a型HCV的患者（n = 304）分为：F评分低的慢性丙型肝炎（CHC）（CHC，n = 110）、终末期肝病（n = 110）、肝硬化（LC）（n = 35）和肝细胞癌（HCC）患者（n = 75），还纳入了HCV感染的自发清除者（n = 84）。代表埃及人群的健康组（n = 100）也纳入了白细胞介素28B的基因分型。通过基于聚合酶链反应的限制性片段长度多态性（PCR-RFLP）分析对从所有个体提取的纯化基因组DNA进行白细胞介素28B基因分型。
与CHC、LC和HCC组相比，健康人群中白细胞介素-28B rs12979860 C/C基因型的频率显著增加（P < 0.0005）（C/C分别为48%、13%、0%和0%）。另一方面，自发清除者中的C/C基因型显著高于健康受试者（P < 0.0005）。在向ESLD进展过程中，检测到C/T等位基因频率有相当显著的增加，同时T/T等位基因频率略有升高。
基因型C/C与急性感染期间的病毒清除相关。从健康受试者到CHC受试者，C/C基因型急剧下降，且在ESLD中完全不存在C/C基因型，这表明该基因型在对抗HCV疾病进展中起核心作用。
