Dataset Information

Gene polymorphisms of cellular senescence marker p21 and disease progression in non-alcohol-related fatty liver disease.

ABSTRACT: 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. To this end, the relation between CDKN1A polymorphism and liver fibrosis was studied in 2 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. Both the UK and Finnish cohorts were significantly different from each other in basic demographics. In the UK cohort, rs762623, of the 6 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. In conclusion, CDKN1A variant rs762623 is associated with the development but not the propagation of progressive liver disease in NAFLD.

SUBMITTER: Aravinthan A

PROVIDER: S-EPMC4050146 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Gene polymorphisms of cellular senescence marker p21 and disease progression in non-alcohol-related fatty liver disease.

Aravinthan Aloysious A Mells George G Allison Michael M Leathart Julian J Kotronen Anna A Yki-Jarvinen Hannele H Daly Ann K AK Day Christopher P CP Anstee Quentin M QM Alexander Graeme G

Cell cycle (Georgetown, Tex.) 20140311 9

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. To this end, the relatio ...[more]

PMID: 24626178

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Project description:The prevalence of nonalcoholic fatty liver disease (NAFLD) is estimated to be 26.3% among the US population. A subset of this population exhibits an aggressive histological phenotype, nonalcoholic steatohepatitis (NASH) with ≥ stage 2 fibrosis, which may progress to cirrhosis. The definition of NAFLD excludes excessive alcohol intake, which is well known to cause alcoholic liver disease and will not be discussed here. Most NAFLD clinical trials use ~14 drinks per week as the cutoff for excessive alcohol intake. Alcohol consumption below this threshold, which we define as moderate alcohol consumption, is common in the US. According to the 2012 Behavioral Risk Factor Surveillance System (BRFSS), 56% of the US adult population consume alcohol, but only 8.2% report drinking heavily and 18.3% report binge drinking. The American Association for the Study of Liver Diseases (AASLD) Practice Guidance of 2018 states that there are insufficient data to make a recommendation with regard to moderate alcohol consumption in patients with NAFLD, citing a lack of longitudinal studies that examine the impact of moderate alcohol consumption on disease progression and its extrahepatic harms versus benefits, specifically in individuals with established NAFLD. NAFLD prevalence studies have generally noted a negative correlation between modest alcohol consumption and NAFLD. However, prevalence studies have limited application to patients with established NAFLD who present to the clinic. There can also be many confounding factors, because modest alcohol consumption is also negatively associated with some NAFLD risk factors, and those risk factors may not be adequately adjusted for in analyses. The prevalence of NASH with significant fibrosis (≥ F2) is more important because this is the group that is believed to have progressive disease. Thus, cohort studies of disease progression are more important from the patient's standpoint. Because these patients have already developed NAFLD or NASH, their interest lies in their odds of disease progression if they have moderate alcohol consumption compared to abstinence. It is also noteworthy that cardiovascular disease is the most important cause of death among patients with NAFLD. Moderate alcohol consumption has been associated with a reduction in overall mortality, but mostly in cardiovascular mortality. However, this protective effect has not been demonstrated specifically in patients with NAFLD.

Dataset Information

Gene polymorphisms of cellular senescence marker p21 and disease progression in non-alcohol-related fatty liver disease.

Publications

Gene polymorphisms of cellular senescence marker p21 and disease progression in non-alcohol-related fatty liver disease.

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