Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, 2055, Montevideo, Mataojo, Uruguay.
Clínica de Gastroenterología, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, 11600, Montevideo, Uruguay.
Virol J. 2018 Mar 2;15(1):40. doi: 10.1186/s12985-018-0946-2.
Host single-nucleotide polymorphisms (SNPs) near the interleukin 28B (IL28B) locus are associated with sustained virological response to antiviral therapy and with spontaneous Hepatitis C Virus (HCV) clearance. Prevalence of these SNPs varies depending on ethnicity. The impact of IL28B SNPs in HCV-infected patients is currently unknown in Uruguay. Therefore, the aim of this study was to evaluate and compare the distribution of polymorphisms in the IL28B gene (rs12979860 and rs8099917) among HCV-infected patients and healthy individuals in Uruguay and thus assess their possible association with the establishment of HCV infection.
DNA was recovered from 92 non-infected individuals and 78 HCV-infected patients and SNPs were determined by RFLP and allelic discrimination by real-time PCR.
The distribution of rs12979860 genotypes for the infected population was 29.5%-CC, 47.4%-CT and 23.1%-TT and for the control group 45.7%, 42.4% and 11.9%, respectively. Prevalence in both infected and uninfected individuals is similar to that reported in other countries with admixed populations. The distribution of rs8099917 genotypes for the infected population was 57.7%-TT, 27.2%-TG and 14.1%-GG and for the control group 60.9%, 33.7% and 5.4%, respectively. The comparison of rs12979860 genotype distribution between the two populations evidenced a higher prevalence of the favourable genotype (CC) in the uninfected control group (p < 0.05). Additionally, results generated using logistic regression analysis show that individuals carrying rs12979860-TT or CT genotypes have a higher likelihood of developing chronic hepatitis upon infection with HCV, when compared to CC carriers, considering rs8099917 genotype as constant.
Patients with HCV infection have a statistically significant lower prevalence of the favourable rs12979860 genotype when compared to uninfected individuals; therefore we can establish that only IL28B rs12979860-CT and TT genotypes seem to contribute to the occurrence of chronic HCV infection in the cohort of Uruguayan population studied. Considering that a trend towards a higher frequency of "good" response genotypes was observed in responder patients, we believe that IL28B rs12979860 genotyping could be a useful tool for predicting different therapies outcome, including in the DAA era.
白细胞介素 28B（IL28B）基因座附近的宿主单核苷酸多态性（SNP）与抗病毒治疗的持续病毒学应答和自发性丙型肝炎病毒（HCV）清除有关。这些 SNP 的流行率因种族而异。IL28B SNP 在 HCV 感染患者中的影响目前在乌拉圭尚不清楚。因此，本研究的目的是评估和比较 IL28B 基因（rs12979860 和 rs8099917）多态性在 HCV 感染患者和乌拉圭健康个体中的分布，并评估其与 HCV 感染建立的可能关联。
从 92 名非感染者和 78 名 HCV 感染者中提取 DNA，并通过 RFLP 和实时 PCR 等位基因鉴别来确定 SNPs。
感染人群 rs12979860 基因型的分布为 29.5%-CC、47.4%-CT 和 23.1%-TT，对照组分别为 45.7%、42.4%和 11.9%。感染和未感染个体的患病率与混合人群的其他国家相似。感染人群 rs8099917 基因型的分布为 57.7%-TT、27.2%-TG 和 14.1%-GG，对照组分别为 60.9%、33.7%和 5.4%。对两组人群 rs12979860 基因型分布的比较表明，未感染对照组中有利基因型（CC）的流行率更高（p<0.05）。此外，使用逻辑回归分析生成的结果表明，与 CC 携带者相比，携带 rs12979860-TT 或 CT 基因型的个体在感染 HCV 后更有可能发展为慢性肝炎，同时考虑 rs8099917 基因型为常数。
与未感染者相比，HCV 感染患者 rs12979860 有利基因型的流行率有统计学意义降低；因此，我们可以确定只有 IL28B rs12979860-CT 和 TT 基因型似乎有助于在研究的乌拉圭人群中发生慢性 HCV 感染。考虑到在应答者患者中观察到“良好”反应基因型的频率较高的趋势，我们认为 IL28B rs12979860 基因分型可能是预测不同治疗结果的有用工具，包括在 DAA 时代。
