Origa Raffaella, Marceddu Giuseppe, Danjou Fabrice, Perseu Luciana, Satta Stefania, Demartis Franca Rosa, Piga Antonio, Longo Filomena, Lai Maria-Eliana, Vacquer Stefania, Galanello Renzo
Clinica Pediatrica 2a, Dipartimento di Sanità Pubblica, Medicina Clinica e Molecolare-Università di Cagliari, Ospedale Regionale Microcitemie ASL8, Cagliari, Italy.
Istituto di Ricerca Genetica e Biomedica (IRGB) CNR, Cagliari, Italy.
Ann Hepatol. 2015 May-Jun;14(3):389-95.
BACKGROUND AND RATIONALE FOR THE STUDY: Genome-wide association studies have identified host genetic variation to be critical for spontaneous clearance and treatment response in patients infected with hepatitis C virus. Recently, the role of the IFNL3 polymorphisms in influencing the spontaneous clearance of HCV, the response to interferon and the progression of liver fibrosis, was also demonstrated in patients with thalassemia major infected by genotype 1b. In the present study we retrospectively analyzed 368 anti-HCV positive patients with beta-thalassemia at two Italian major centers in Cagliari and Torino.
C/C variant of polymorphism rs12979860 was related to response to interferon treatment and, above all, to spontaneous clearance of the virus. However, the positive predictive power was stronger for viral persistence than spontaneous clearance and in such respect the TT allele was more predictive than CC. The methylation associated polymorphism rs4803221 had independent effects with respect to rs12979860 and the haplotype tagged by SNP rs12979860 and rs4803221 significantly could improve the viral clearance prediction in infected patients. Neither necroinflammation or bilirubin values in the chronic phase of the hepatitis C were related to IFNL3 polymorphisms. No relation among IFNL3 polymorphisms and fibrosis stage directly shown by the liver biopsy was found.
Also in thalassemia the SNPs on chromosome 19q13 closely associates with spontaneous and treatment-induced HCV clearance. The viral clearance prediction is significantly improved by the haplotype tagged by SNP rs12979860 and rs4803221. Neither necroinflammation, bilirubin values or fibrosis stage seem to be related to IFNL3 polymorphisms.
研究背景与原理：全基因组关联研究已确定宿主基因变异对于丙型肝炎病毒感染患者的自发清除和治疗反应至关重要。最近，在感染1b基因型的重型地中海贫血患者中，也证实了IFNL3基因多态性在影响HCV自发清除、对干扰素的反应以及肝纤维化进展方面的作用。在本研究中，我们回顾性分析了意大利卡利亚里和都灵两个主要中心的368例抗HCV阳性的β地中海贫血患者。
多态性rs12979860的C/C变异与干扰素治疗反应相关，最重要的是与病毒的自发清除相关。然而，对于病毒持续存在的阳性预测能力比对自发清除更强，在这方面，TT等位基因比CC更具预测性。与甲基化相关的多态性rs4803221相对于rs12979860具有独立作用，并且由SNP rs12979860和rs4803221标记的单倍型能够显著改善对感染患者病毒清除的预测。丙型肝炎慢性期的坏死性炎症或胆红素值均与IFNL3基因多态性无关。未发现IFNL3基因多态性与肝活检直接显示的纤维化阶段之间存在关联。
在重型地中海贫血患者中，19q13染色体上的单核苷酸多态性（SNP）也与HCV的自发清除及治疗诱导清除密切相关。由SNP rs12979860和rs4803221标记的单倍型可显著改善病毒清除的预测。坏死性炎症、胆红素值或纤维化阶段似乎均与IFNL3基因多态性无关。
