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Gene Polymorphisms of Cellular Senescence Marker P21 and Disease Progression in Non-Alcohol-Related Fatty Liver Disease

Lookup NU author(s): Julian Leathart, Professor Ann Daly, Professor Chris Day, Professor Quentin Anstee

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Abstract

Background & aim: Non-alcohol-related fatty liver disease (NAFLD) encompasses a wide spectrum ranging from steatosis alone to steatohepatitis and fibrosis. Presence of steatohepatitis and fibrosis are key hallmarks of disease progression. Previous studies have demonstrated an association between hepatocyte p21 expression and fibrosis stage in NAFLD. The aim of this study is to investigate the association between the variants of CDKN1A, which encodes p21, and disease progression in NAFLD. Methods: The relation of CDKN1A polymorphism with steatohepatitis and fibrosis was studied in two cohorts of biopsy-proven NAFLD patients from UK (n=323) and Finland (n=123). Genotyping was performed using DNA isolated from lymphocytes collected at the time of liver biopsy. The findings of the UK cohort were tested in the Finnish cohort. Results: Both the UK and Finnish cohorts were significantly different from each other in basic demographics. In the UK cohort, rs762623 of the six SNPs across CDKN1A tested was significantly associated with disease progression in NAFLD. This association was confirmed in the Finnish cohort. Despite the influence on fibrosis development, SNPs across CDKN1A did not affect the progression of liver fibrosis. Conclusion: CDKN1A variant rs762623 is associated with the development but not the propagation of progressive liver disease in NAFLD.


Publication metadata

Author(s): Aravinthan A, Mells G, Allison M, Leathart J, Kotronen A, Yki-Jarvinen H, Daly AK, Day CP, Anstee QM, Alexander G

Publication type: Article

Publication status: Published

Journal: Cell Cycle

Year: 2014

Volume: 13

Issue: 9

Pages: 1489-1494

Print publication date: 11/03/2014

Date deposited: 01/03/2015

ISSN (print): 1538-4101

ISSN (electronic): 1551-4005

Publisher: Landes Bioscience

URL: http://dx.doi.org/10.4161/cc.28471

DOI: 10.4161/cc.28471

PubMed id: 24626178


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