Interferon-λ rs12979860 genotype and liver fibrosis in viral and non-viral chronic liver disease.
Interferon-λ rs12979860 genotype and liver fibrosis in viral and non-viral chronic liver disease.
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DOI：
10.1038/ncomms7422
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发表时间：
2015-03-05
影响因子：
16.6
通讯作者：
Ahlenstiel, Golo
中科院分区：
文献类型：
--
作者：
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
组织纤维化是一个核心病理过程，导致约 45% 的人口死亡，并且可能受到宿主遗传结构的影响。在这里，我们以肝脏疾病为模型，证明干扰素 λ4 (IFNL4) 内含子区域的单核苷酸多态性 (rs12979860) 是纤维化的强有力的预测因子，且与病因无关。在 4,172 名患者的队列中，包括 3,129 名慢性丙型肝炎 (CHC) 患者、555 名慢性乙型肝炎 (CHB) 患者和 488 名非酒精性脂肪肝病 (NAFLD) 患者，携带 rs12979860CC 的患者肝脏炎症和纤维化程度更高。在 CHC 中，携带 rs12979860CC 的患者也具有更高的持续阶段和阶段特异性纤维化进展率（全部 P<0.0001）。 rs12979860 基因型对纤维化的影响在年轻女性中最大，尤其是那些具有 HCV 基因型 3 的女性。这些发现确立了 rs12979860 基因型作为组织炎症和纤维化的强独立于病因学的预测因子。 组织纤维化是发达国家死亡的主要原因。在这里，作者鉴定了干扰素 λ4 内含子区域的遗传变异，它是肝脏炎症和纤维化的强有力预测因子，与肝病病因无关
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. Tissue fibrosis is a major contributor to mortality in the developed world. Here, the authors identify a genetic variant in the intronic region of interferon-λ4 that is a strong predictor of hepatic inflammation and fibrosis, independent of liver disease aetiology
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影响因子：
25.7
作者：
Eslam, Mohammed;Leung, Reynold;Ahlenstiel, Gobo
通讯作者：
Ahlenstiel, Gobo
影响因子：
82.9
作者：
Mehal, Wajahat Z.;Iredale, John;Friedman, Scott L.
通讯作者：
Friedman, Scott L.
影响因子：
30.5
作者：
McFarland, Addle P.;Horner, Stacy M.;Jarret, Abigail;Joslyn, Rochelle C.;Bindewald, Eckart;Shapiro, Bruce A.;Delker, Don A.;Hagedorn, Curt H.;Carrington, Mary;Gale, Michael, Jr.;Savan, Ram
通讯作者：
Savan, Ram
影响因子：
13.5
作者：
Grebely, Jason;Page, Kimberly;Sacks-Davis, Rachel;van der Loeff, Maarten Schim;Rice, Thomas M.;Bruneau, Julie;Morris, Meghan D.;Hajarizadeh, Behzad;Amin, Janaki;Cox, Andrea L.;Kim, Arthur Y.;McGovern, Barbara H.;Schinkel, Janke;George, Jacob;Shoukry, Naglaa H.;Lauer, Georg M.;Maher, Lisa;Lloyd, Andrew R.;Hellard, Margaret;Dore, Gregory J.;Prins, Maria
通讯作者：
Prins, Maria
影响因子：
13.5
作者：
Bedossa, P;Poynard, T
通讯作者：
Poynard, T