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Interleukin-17 haplotyping predicts hepatocellular carcinoma in sofosbuvir, pegylated interferon-alpha-2a & ribavirin treated chronic hepatitis C patients
Virus Research ( IF 2.5 ) Pub Date : 2020-11-07 , DOI: 10.1016/j.virusres.2020.198226
Ahmed M Mostafa 1 , Hesham A Saafan 2 , Ahmed S Al-Tawashi 3 , Muhannad H Kasem 3 , Ahmed M Alaa 3 , Mahmoud M Eltobgy 3 , Ahmed S Moubarak 3 , Manar M Gharib 3 , Mohamed A Awwad 3 , Hazem M Omar 4 , Marwa O El-Derany 1
Affiliation  

Suspect has been directed towards some direct acting antivirals (DAAs) due to their reported association with hepatocellular carcinoma (HCC) development in chronic hepatitis C (CHC) patients. The mechanisms behind HCC development, following CHC treatment, were not well understood and may be linked to genetic variabilities in different patients which affect several cytokine productions involved in angiogenesis and inflammation. Of these variabilities, is the genetic polymorphisms in the interleukin-17 (IL-17) A receptor gene. Being an important pleiotropic cytokine, this study aimed to investigate the association between haplotypes in IL-17A receptor rs2275913 and rs3819024 and development of HCC in CHC patients treated with either triple therapy (sofosbuvir (SOF), pegylated interferon-alpha-2a (Peg-IFNα-2a) & ribavirin(RBV)) or with dual therapy (Peg-IFNα-2a&RBV). A cohort of 100 CHC patients was recruited in this study. Samples were tested for single nucleotide polymorphism (SNPs) in IL-17A receptor (rs2275913 and rs3819024) using TaqMan Genotyping assay. Our results showed that the presence of G-G haplotype in IL-17A (rs2275913& rs3819024) is inversely associated with HCC development in patients receiving triple therapy. While, high serum AFP levels are directly associated with HCC development in patients receiving triple therapy. However, in patients receiving dual therapy, HCC development was only associated with high serum alpha fetoprotein (AFP) levels and was not correlated to any specific allele in our studied SNPs. Such results highlight the importance of IL17A receptor gene haplotyping in the prediction of HCC development in patients receiving triple therapy. These results will aid in performing tailored, personalized strategy for CHC treatment.



中文翻译:

白细胞介素 17 单体型可预测索非布韦、聚乙二醇干扰素-α-2a 和利巴韦林治疗慢性丙型肝炎患者的肝细胞癌

由于据报道它们与慢性丙型肝炎 (CHC) 患者的肝细胞癌 (HCC) 发展有关,因此怀疑直接作用于抗病毒药物 (DAA)。在接受 CHC 治疗后,HCC 发展背后的机制尚不清楚,可能与不同患者的遗传变异有关,遗传变异会影响涉及血管生成和炎症的几种细胞因子的产生。在这些变异性中,有白介素-17 (IL-17) A 受体基因的遗传多态性。作为一种重要的多效细胞因子,本研究旨在调查 IL-17A 受体 rs2275913 和 rs3819024 的单倍型与接受三联疗法(索非布韦 (SOF)、聚乙二醇化干扰素-α-2a (Peg-干扰素α-2a) & 利巴韦林(RBV))或双重治疗(Peg-IFNα-2a&RBV)。本研究招募了 100 名 CHC 患者。使用 TaqMan 基因分型分析测试样品的 IL-17A 受体(rs2275913 和 rs3819024)中的单核苷酸多态性 (SNP)。我们的结果表明,在接受三联疗法的患者中,IL-17A(rs2275913 和 rs3819024)中 GG 单倍型的存在与 HCC 的发展呈负相关。而在接受三联疗法的患者中,高血清 AFP 水平与 HCC 的发展直接相关。然而,在接受双重治疗的患者中,HCC 的发展仅与高血清甲胎蛋白 (AFP) 水平相关,与我们研究的 SNP 中的任何特定等位基因无关。这些结果强调了 IL17A 受体基因单倍型分析在预测接受三联疗法的患者的 HCC 发展中的重要性。这些结果将有助于为 CHC 治疗执行量身定制的个性化策略。

更新日期:2020-11-25
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