Human genetics of metabolic dysfunction–associated steatotic liver disease: from variants to cause to precision treatment DOI Creative Commons
Vincent Chen, Annapurna Kuppa, Antonino Oliveri

et al.

Journal of Clinical Investigation, Journal Year: 2025, Volume and Issue: 135(7)

Published: March 31, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by increased hepatic steatosis with cardiometabolic and a leading cause of advanced disease. We review here the genetic basis MASLD. The variants most consistently associated implicate genes involved in lipoprotein input or output, glucose metabolism, adiposity/fat distribution, insulin resistance, mitochondrial/ER biology. distinct mechanisms which these promote result effects on that may be best suited to precision medicine. Recent work gene-environment interactions has shown risk not fixed exacerbated attenuated modifiable (diet, exercise, alcohol intake) nonmodifiable environmental factors. Some steatosis-associated variants, notably those patatin-like phospholipase domain-containing 3 (PNPLA3) transmembrane 6 superfamily member 2 (TM6SF2), are developing adverse liver-related outcomes provide information beyond clinical stratification tools, especially individuals at intermediate high for Future better characterize heterogeneity combining genetics factors holistically predict develop therapies based required.

Language: Английский

Disparities for Hispanic Adults With Metabolic Dysfunction-associated Steatotic Liver Disease in the United States: A Systematic Review and Meta-analysis DOI
Kaleb Tesfai, Jordan Pace,

Nora El-Newihi

et al.

Clinical Gastroenterology and Hepatology, Journal Year: 2024, Volume and Issue: unknown

Published: July 1, 2024

Language: Английский

Citations

9
The Proteomics of MASLD Progression: Insights From Functional Analysis to Drive the Development of New Therapeutic Solutions DOI Creative Commons
Carlos J. Pirola, Tomas Fernández Gianotti, Silvia Sookoian

et al.

Alimentary Pharmacology & Therapeutics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading chronic worldwide, with alarming prevalence reaching epidemic proportions.

Language: Английский

Citations

1
Recent advances in MASLD genetics: Insights into disease mechanisms and the next frontiers in clinical application DOI Creative Commons
Vincent Chen, Graham F. Brady

Hepatology Communications, Journal Year: 2025, Volume and Issue: 9(1)

Published: Jan. 1, 2025

Metabolic dysfunction–associated steatotic liver disease (MASLD) is the most common chronic in world and a growing cause of liver-related morbidity mortality. Yet, at same time, our understanding pathophysiology genetic underpinnings this increasingly yet heterogeneous has increased dramatically over last 2 decades, with potential to lead meaningful clinical interventions for patients. We have now seen first pharmacologic therapy approved treatment MASLD, multiple other treatments are currently under investigation—including gene-targeted RNA therapies that directly extend from advances MASLD genetics. Here we review recent genetics, some key pathophysiologic insights human genetics provided, ways which may inform practice field near future.

Language: Английский

Citations

1
Unraveling Metabolic Dysfunction-Associated Steatotic Liver Disease Through the Use of Omics Technologies DOI Open Access
Maria V. Bourganou, Maria Chondrogianni, Ioannis Kyrou

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1589 - 1589

Published: Feb. 13, 2025

Non-alcoholic fatty liver disease (NAFLD), now referred to as metabolic dysfunction-associated steatotic (MASLD), is the most prevalent disorder globally, linked obesity, type 2 diabetes, and cardiovascular risk. Understanding its potential progression from simple steatosis cirrhosis hepatocellular carcinoma (HCC) crucial for patient management treatment strategies. The disease's complexity requires innovative approaches early detection personalized care. Omics technologies-such genomics, transcriptomics, proteomics, metabolomics, exposomics-are revolutionizing study of MASLD. These high-throughput techniques allow a deeper exploration molecular mechanisms driving progression. Genomics can identify genetic predispositions, whilst transcriptomics proteomics reveal changes in gene expression protein profiles during evolution. Metabolomics offers insights into alterations associated with MASLD, while exposomics links environmental exposures MASLD pathology. By integrating data various omics platforms, researchers map out intricate biochemical pathways involved This review discusses roles technologies enhancing understanding highlights diagnostic therapeutic targets within spectrum, emphasizing need non-invasive tools staging development.

Language: Английский

Citations

1
Human genetics of metabolic dysfunction–associated steatotic liver disease: from variants to cause to precision treatment DOI Creative Commons
Vincent Chen, Annapurna Kuppa, Antonino Oliveri

et al.

Journal of Clinical Investigation, Journal Year: 2025, Volume and Issue: 135(7)

Published: March 31, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by increased hepatic steatosis with cardiometabolic and a leading cause of advanced disease. We review here the genetic basis MASLD. The variants most consistently associated implicate genes involved in lipoprotein input or output, glucose metabolism, adiposity/fat distribution, insulin resistance, mitochondrial/ER biology. distinct mechanisms which these promote result effects on that may be best suited to precision medicine. Recent work gene-environment interactions has shown risk not fixed exacerbated attenuated modifiable (diet, exercise, alcohol intake) nonmodifiable environmental factors. Some steatosis-associated variants, notably those patatin-like phospholipase domain-containing 3 (PNPLA3) transmembrane 6 superfamily member 2 (TM6SF2), are developing adverse liver-related outcomes provide information beyond clinical stratification tools, especially individuals at intermediate high for Future better characterize heterogeneity combining genetics factors holistically predict develop therapies based required.

Language: Английский

Citations

1