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PNPLA3 I148M polymorphism and progressive liver disease
Open accessAbstract
The 148 Isoleucine to Methionine protein variant (I148M) of patatin-like phospholipase domain-containing 3 (PNPLA3), a protein is expressed in the liver and is involved in lipid metabolism, has recently been identified as a major determinant of liver fat content. Several studies confirmed that the I148M variant predisposes towards the full spectrum of liver damage associated with fatty liver: from simple steatosis to steatohepatitis and progressive fibrosis. Furthermore, the I148M variant represents a major determinant of progression of alcohol related steatohepatitis to cirrhosis, and to influence fibrogenesis and related clinical outcomes in chronic hepatitis C virus hepatitis, and possibly chronic hepatitis B virus hepatitis, hereditary hemochromatosis and primary sclerosing cholangitis. All in all, studies suggest that the I148M polymorphism may represent a general modifier of fibrogenesis in liver diseases. Remarkably, the effect of the I148M variant on fibrosis was independent of that on hepatic steatosis and inflammation, suggesting that it may affect both the quantity and quality of hepatic lipids and the biology of non-parenchymal liver cells besides hepatocytes, directly promoting fibrogenesis. Therefore, PNPLA3 is a key player in liver disease progression. Assessment of the I148M polymorphism will possibly inform clinical practice in the future, whereas the determination of the effect of the 148M variant will reveal mechanisms involved in hepatic fibrogenesis.
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“As for predisposing genetic factors, the I148M PNPLA3 single-nucleotide polymorphism (SNP) has been identified as a major common genetic determinant of MASH severity and outcome(220), while several other gene variants are also likely to modify”
From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [220]
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Metadata
- Authors
- Dongiovanni, P.
- Affiliations
- University of Milan (IT)
- Corresponding author
- Dongiovanni, Paola
- ORCID
- Dongiovanni, Paola
- Venue
- World Journal of Gastroenterology
- Publisher
- Baishideng Publishing Group Inc.
- Published
- 2013
- Volume
- 19
- Issue
- 41
- Pages
- 6969
- ISSN
- 1007-9327 (ISSN-L)
- PMC
- PMC3819533
- OpenAlex
- W2031119940
- Cited by
- 252
- References
- 103
- Citations by year
- 2026: 11 · 2025: 18 · 2024: 10 · 2023: 26 · 2022: 19 · 2021: 24 · 2020: 25 · 2019: 12 · 2018: 17 · 2017: 23 · 2016: 21 · 2015: 31 · 2014: 15
- FWCI
- 2.65
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- World Journal of Gastroenterology (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Keywords
- PNPLA3, I148M polymorphism, hepatic steatosis, steatohepatitis, liver fibrosis, fibrogenesis, liver cirrhosis, chronic hepatitis C, chronic hepatitis B, hereditary hemochromatosis, primary sclerosing cholangitis, genetic susceptibility, non-parenchymal liver cells, lipid metabolism
- MeSH terms
- Acyltransferases, Fatty Liver, Fatty Liver, Alcoholic, Hemochromatosis, Carcinoma, Hepatocellular, Humans, Lipase, Liver Cirrhosis, Liver Cirrhosis, Alcoholic, Liver Neoplasms, Membrane Proteins, Phenotype, Polymorphism, Genetic, Risk Factors, Cholangitis, Sclerosing, Disease Progression, Hepatitis B, Chronic, Hepatitis C, Chronic, Genetic Predisposition to Disease, Phospholipases A2, Calcium-Independent, Non-alcoholic Fatty Liver Disease
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