scholarly journals Nuclear lamina genetic variants, including a truncated LAP2, in twins and siblings with nonalcoholic fatty liver disease

Hepatology ◽  
2018 ◽  
Vol 67 (5) ◽  
pp. 1710-1725 ◽  
Author(s):  
Graham F. Brady ◽  
Raymond Kwan ◽  
Peter J. Ulintz ◽  
Phirum Nguyen ◽  
Shirin Bassirian ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Genetic Variants ◽  
Fatty Liver Disease ◽  
Nuclear Lamina ◽  
Nonalcoholic Fatty Liver

scholarly journals The Pathogenesis of Nonalcoholic Fatty Liver Disease: Interplay between Diet, Gut Microbiota, and Genetic Background

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Jinsheng Yu ◽  
Sharon Marsh ◽  
Junbo Hu ◽  
Wenke Feng ◽  
Chaodong Wu
Keyword(s):  
Liver Disease ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Genetic Variants ◽  
Genetic Background ◽  
Fatty Liver Disease ◽  
Genome Wide Association Studies ◽  
Nonalcoholic Fatty Liver ◽  
Pathogenic Mechanisms

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, and it comprises a spectrum of hepatic abnormalities from simple hepatic steatosis to steatohepatitis, fibrosis, cirrhosis, and liver cancer. While the pathogenesis of NAFLD remains incompletely understood, a multihit model has been proposed that accommodates causal factors from a variety of sources, including intestinal and adipose proinflammatory stimuli acting on the liver simultaneously. Prior cellular and molecular studies of patient and animal models have characterized several common pathogenic mechanisms of NAFLD, including proinflammation cytokines, lipotoxicity, oxidative stress, and endoplasmic reticulum stress. In recent years, gut microbiota has gained much attention, and dysbiosis is recognized as a crucial factor in NAFLD. Moreover, several genetic variants have been identified through genome-wide association studies, particularly rs738409 (Ile748Met) inPNPLA3and rs58542926 (Glu167Lys) inTM6SF2, which are critical risk alleles of the disease. Although a high-fat diet and inactive lifestyles are typical risk factors for NAFLD, the interplay between diet, gut microbiota, and genetic background is believed to be more important in the development and progression of NAFLD. This review summarizes the common pathogenic mechanisms, the gut microbiota relevant mechanisms, and the major genetic variants leading to NAFLD and its progression.

Genetic variants in STAT3 are associated with nonalcoholic fatty liver disease

Cytokine ◽  
2008 ◽  
Vol 44 (1) ◽  
pp. 201-206 ◽  
Author(s):  
Silvia Sookoian ◽  
Gustavo Castaño ◽  
Tomas Fernández Gianotti ◽  
Carolina Gemma ◽  
María Soledad Rosselli ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Genetic Variants ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver

scholarly journals The association of genetic polymorphisms with nonalcoholic fatty liver disease in a longitudinal study

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Goh Eun Chung ◽  
Eunsoon Shin ◽  
Min-Sun Kwak ◽  
Jong In Yang ◽  
Jong-Eun Lee ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Genetic Variants ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver ◽  
Genome Wide ◽  
A Genome ◽  
Validation Set

Abstract Background Several genetic variants are known to be associated with nonalcoholic fatty liver disease (NAFLD). We aimed to evaluate the longitudinal associations between genetic variants and NAFLD. Methods We performed a genome-wide association study (GWAS) in Korean individuals who underwent repeated health check-ups. NAFLD was defined by ultrasonography and exclusion of secondary causes. Results The subjects had a median age of 50.0 years, and 54.8% were male. The median follow-up duration was 39 months. Among the 3905 subjects without NAFLD at baseline, 874 (22.4%) subjects developed NAFLD, and among the 1818 subjects with NAFLD at baseline, NAFLD regressed in 336 (18.5%) subjects during the follow-up period. After adjusting for age, sex and body mass index, no single-nucleotide polymorphism (SNP) passed Bonferroni correction for genome-wide significance in the development or regression of NAFLD. Among the SNPs that passed the genome-wide suggestiveness threshold (p = 1E-04) in the discovery set in the GWAS, only 1 SNP (rs4906353) showed an association with the development of NAFLD, with marginal significance in the validation set (p-value, discovery set = 9.68E-5 and validation set = 0.00531). Conclusions This exploratory study suggests that longitudinal changes in NAFLD are not associated with genetic variants in the Korean population. These findings provide new insight into genetic mechanisms in the pathogenesis of NAFLD.

scholarly journals Novel Insights into the Genetic Landscape of Nonalcoholic Fatty Liver Disease

2019 ◽  
Vol 16 (15) ◽  
pp. 2755 ◽  
Author(s):  
Taliento ◽  
Dallio ◽  
Federico ◽  
Prati ◽  
Valenti
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Genetic Variants ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Liver Disorder ◽  
Nonalcoholic Fatty Liver ◽  
Retinol Metabolism

Nonalcoholic fatty liver disease (NAFLD), the most common liver disorder worldwide, is epidemiologically associated with overweight, insulin resistance features and type 2 diabetes, and can progress to advanced liver fibrosis and hepatocellular carcinoma. Genetic factors play an important role in the development of NAFLD, which is a multifactorial disease. Several common naturally occurring variants modulating lipid and retinol metabolism in hepatocytes predispose to NAFLD development and progression, in particular those in PNPLA3, TM6SF2, MBOAT7, and HSD17B13. In addition, genetic variants that protect hepatic cells from oxidative stress modulate the susceptibility to progressive NAFLD. Although the molecular mechanisms linking these genetic variants with liver disease are not yet fully understood, hepatic fat has emerged as a major driver of the disease, while altered retinol metabolism and mitochondrial oxidative stress play a role in determining the development of advanced NAFLD.

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