Eslam Mohammed, Hashem Ahmed M, Leung Reynold, Romero-Gomez Manuel, Berg Thomas, Dore Gregory J, Chan Henry L K, Irving William L, Sheridan David, Abate Maria L, Adams Leon A, Mangia Alessandra, Weltman Martin, Bugianesi Elisabetta, Spengler Ulrich, Shaker Olfat, Fischer Janett, Mollison Lindsay, Cheng Wendy, Powell Elizabeth, Nattermann Jacob, Riordan Stephen, McLeod Duncan, Armstrong Nicola J, Douglas Mark W, Liddle Christopher, Booth David R, George Jacob, Ahlenstiel Golo
Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Sydney, New South Wales 2145, Australia.
Faculty of Engineering, Department of Systems and Biomedical Engineering, Minia University, Minia 6111, Egypt.
Nat Commun. 2015 Mar 5;6:6422. doi: 10.1038/ncomms7422.
Tissue fibrosis is a core pathologic process that contributes to mortality in ~45% of the population and is likely to be influenced by the host genetic architecture. Here we demonstrate, using liver disease as a model, that a single-nucleotide polymorphism (rs12979860) in the intronic region of interferon-λ4 (IFNL4) is a strong predictor of fibrosis in an aetiology-independent manner. In a cohort of 4,172 patients, including 3,129 with chronic hepatitis C (CHC), 555 with chronic hepatitis B (CHB) and 488 with non-alcoholic fatty liver disease (NAFLD), those with rs12979860CC have greater hepatic inflammation and fibrosis. In CHC, those with rs12979860CC also have greater stage-constant and stage-specific fibrosis progression rates (P<0.0001 for all). The impact of rs12979860 genotypes on fibrosis is maximal in young females, especially those with HCV genotype 3. These findings establish rs12979860 genotype as a strong aetiology-independent predictor of tissue inflammation and fibrosis.
组织纤维化是一种核心病理过程，约45%的人群死亡与之相关，且可能受宿主基因结构影响。在此，我们以肝病为模型证明，干扰素λ4（IFNL4）内含子区域的单核苷酸多态性（rs12979860）以病因独立的方式，是纤维化的有力预测指标。在一个由4172名患者组成的队列中，包括3129例慢性丙型肝炎（CHC）患者、555例慢性乙型肝炎（CHB）患者和488例非酒精性脂肪性肝病（NAFLD）患者，携带rs12979860CC的患者有更严重的肝脏炎症和纤维化。在CHC患者中，携带rs12979860CC的患者也有更高的分期恒定和分期特异性纤维化进展率（所有P<0.0001）。rs12979860基因型对纤维化的影响在年轻女性中最大，尤其是那些感染丙型肝炎病毒3型的女性。这些发现确立了rs12979860基因型是组织炎症和纤维化的有力病因独立预测指标。
