https://scholars.lib.ntu.edu.tw/handle/123456789/633799
標題: | Clonal haematopoiesis and risk of chronic liver disease | 作者: | Wong, Waihay J Emdin, Connor Bick, Alexander G Zekavat, Seyedeh M Niroula, Abhishek Pirruccello, James P Dichtel, Laura Griffin, Gabriel Uddin, Md Mesbah Gibson, Christopher J Kovalcik, Veronica Lin, Amy E McConkey, Marie E Vromman, Amelie Sellar, Rob S Kim, Peter G Agrawal, Mridul Weinstock, Joshua Long, Michelle T Yu, Bing Banerjee, Rajarshi Nicholls, Rowan C Dennis, Andrea Kelly, Matt Loh, Po-Ru McCarroll, Steve Boerwinkle, Eric Vasan, Ramachandran S Jaiswal, Siddhartha Johnson, Andrew D Chung, Raymond T Corey, Kathleen Levy, Daniel Ballantyne, Christie Ebert, Benjamin L Natarajan, Pradeep YI-CHENG CHANG LEE-MING CHUANG et al. |
公開日期: | 四月-2023 | 卷: | 616 | 期: | 7958 | 起(迄)頁: | 747 - 754 | 來源出版物: | Nature | 摘要: | Chronic liver disease is a major public health burden worldwide1. Although different aetiologies and mechanisms of liver injury exist, progression of chronic liver disease follows a common pathway of liver inflammation, injury and fibrosis2. Here we examined the association between clonal haematopoiesis of indeterminate potential (CHIP) and chronic liver disease in 214,563 individuals from 4 independent cohorts with whole-exome sequencing data (Framingham Heart Study, Atherosclerosis Risk in Communities Study, UK Biobank and Mass General Brigham Biobank). CHIP was associated with an increased risk of prevalent and incident chronic liver disease (odds ratio = 2.01, 95% confidence interval (95% CI) [1.46, 2.79]; P < 0.001). Individuals with CHIP were more likely to demonstrate liver inflammation and fibrosis detectable by magnetic resonance imaging compared to those without CHIP (odds ratio = 1.74, 95% CI [1.16, 2.60]; P = 0.007). To assess potential causality, Mendelian randomization analyses showed that genetic predisposition to CHIP was associated with a greater risk of chronic liver disease (odds ratio = 2.37, 95% CI [1.57, 3.6]; P < 0.001). In a dietary model of non-alcoholic steatohepatitis, mice transplanted with Tet2-deficient haematopoietic cells demonstrated more severe liver inflammation and fibrosis. These effects were mediated by the NLRP3 inflammasome and increased levels of expression of downstream inflammatory cytokines in Tet2-deficient macrophages. In summary, clonal haematopoiesis is associated with an elevated risk of liver inflammation and chronic liver disease progression through an aberrant inflammatory response. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/633799 | ISSN: | 0028-0836 1476-4687 |
DOI: | 10.1038/s41586-023-05857-4 |
顯示於: | 醫學系 |
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