De Re Valli, Tornesello Maria Lina, De Zorzi Mariangela, Caggiari Laura, Pezzuto Francesca, Leone Patrizia, Racanelli Vito, Lauletta Gianfranco, Gragnani Laura, Buonadonna Angela, Vaccher Emanuela, Zignego Anna Linda, Steffan Agostino, Buonaguro Franco M
Centro di Riferimento Oncologico, Cancer Institute, Aviano, Italy.
Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale", Naples, Italy.
Front Microbiol. 2019 Mar 15;10:475. doi: 10.3389/fmicb.2019.00475. eCollection 2019.
Polymorphisms in the immune response genes can contribute to clearance of hepatitis C virus (HCV) infection but also mediate liver inflammation and cancer pathogenesis. This study aimed to investigate the association of polymorphisms in PD-1 (PDCD1), IFNL3 (IL28B), and TLR2 immune related genes in chronic HCV patients with different hepatic and lymphoproliferative HCV-related diseases. Selected PDCD1, IFNL3, and TLR2 genes were tested by molecular approaches in 450 HCV-positive patients with increasing severity of underlying liver diseases [including chronic infection (CHC), cirrhosis and hepatocellular carcinoma (HCC)], in 238 HCV-positive patients with lymphoproliferative diseases [such as cryoglobulinemia and non-Hodgkin lymphoma (NHL)] and in 94 blood donors (BD). While the rs12979860 IFNL3 T allele was found a good marker associated with HCV-outcome together with the rs111200466 TLR2 del variant, the rs10204525 PD-1.6 A allele was found to have an insignificant role in patients with HCV-related hepatic disorders. Though in Asian patients the combination of IFNL3 and PD-1.6 markers better define the HCV-related outcomes, in our series of Caucasian patients the PD-1.6 A-allele variant was observed very rarely. Differences in the incidence of HCV-related HCC and clinical response between Asians and Europeans may be partially due to the distribution of PD-1.6 genotype that we found divergent between these two populations. On the other hand, we confirmed in this study that the polymorphic variants within IFNL3 and TLR2 immune response genes are significantly associated with HCV-related disease progression in our cohort of Italian patients.
免疫反应基因中的多态性可有助于丙型肝炎病毒（HCV）感染的清除，但也介导肝脏炎症和癌症发病机制。本研究旨在调查慢性HCV患者中，PD-1（PDCD1）、IFNL3（IL28B）和TLR2免疫相关基因的多态性与不同肝脏及淋巴增殖性HCV相关疾病之间的关联。通过分子方法，对450例潜在肝脏疾病严重程度不断增加的HCV阳性患者[包括慢性感染（CHC）、肝硬化和肝细胞癌（HCC）]、238例患有淋巴增殖性疾病[如冷球蛋白血症和非霍奇金淋巴瘤（NHL）]的HCV阳性患者以及94名献血者（BD），检测选定的PDCD1、IFNL3和TLR2基因。虽然发现rs12979860 IFNL3 T等位基因与rs111200466 TLR2缺失变体一样，是与HCV转归相关的良好标志物，但发现rs10204525 PD-1.6 A等位基因在HCV相关肝脏疾病患者中作用不显著。尽管在亚洲患者中，IFNL3和PD-1.6标志物的组合能更好地界定HCV相关转归，但在我们的白种人患者系列中，PD-1.6 A等位基因变体很少观察到。亚洲人和欧洲人之间HCV相关HCC发病率和临床反应的差异，可能部分归因于我们发现的这两个群体之间PD-1.6基因型分布的差异。另一方面，我们在本研究中证实，在我们的意大利患者队列中，IFNL3和TLR2免疫反应基因内的多态性变体与HCV相关疾病进展显著相关。
