ReviewLiver international : official journal of the International Association for the Study of the Liver2025
PNPLA3 I148M Interacts With Environmental Triggers to Cause Human Disease.
Review in Liver international : official journal of the International Association for the Study of the Liver, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Association between PNPLA3 rs738409 and susceptibility to etiology-specific liver cirrhosis: a systematic review and meta-analysis.BMC medical genomics · 2026Pooled it
- Metabolic disorder-MASLD-cardiovascular disease-kidney disease (MMCK) syndrome: an expansion of the Cardiovascular-Kidney-Metabolic (CKM) framework.Cardiovascular diabetology. Endocrinology reports · 2026Review
- Genetics of MASLD: a diabetes perspective.Diabetologia · 2026Review
- PNPLA3 polymorphisms and risk of hepatic and extrahepatic outcomes in MASLD: A meta-analysis of observational studies.JHEP reports : innovation in hepatology · 2026Article
- Selenium and Liver Steatosis and Fibrosis: Opposing Direct and Steatosis-Mediated Associations in a Large Cohort.JGH open : an open access journal of gastroenterology and hepatology · 2026Article
- Interactions Between the Gut Microbiome and Genetic and Clinical Risk Factors for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in Patients with Type 2 Diabetes Mellitus from Different Geographical Regions of Argentina.Life (Basel, Switzerland) · 2026Article
- TERT rs10069690 variant is linked to reduced cholangiocarcinoma incidence but adverse prognosis in patients undergoing resection.eGastroenterology · 2026Article
- Metabolic dysfunction associated steatotic liver disease: mechanisms, diagnosis, and management in adults.BMJ medicine · 2026Review
- Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Mechanisms, Clinical Implications and Therapeutic Advances.Endocrinology, diabetes & metabolism · 2025Review
- Metabolic Dysfunction-Associated Steatotic Liver Disease in a Patient with Phelan-McDermid Syndrome.Life (Basel, Switzerland) · 2025Article
- Fifteen Years of PNPLA3: Transforming Hepatology Through Human Genetics.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Novel Amido Heteroaromatic Compounds as 17βHSD13 Inhibitors for Treating Liver Disease, Namely, NASH.ACS medicinal chemistry letters · 2025Article
- Liver-Kidney Crosstalk in Major Pediatric Diseases: Unraveling the Complexities and Clinical Challenges.Journal of clinical medicine · 2025Review
- The Role of Extracellular Vesicles in the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease and Other Liver Diseases.International journal of molecular sciences · 2025Review
- Human genetics of metabolic dysfunction-associated steatotic liver disease: from variants to cause to precision treatment.The Journal of clinical investigation · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
Abstract
backgroundMetabolic dysfunction-associated steatotic liver disease (MASLD) affects up to 30% of Western populations. While obesity is a recognized risk factor, MASLD does not develop in all obese individuals, highlighting the need to understand genetic and environmental interactions. The PNPLA3 I148M variant has been identified as a key genetic risk factor, significantly increasing the likelihood of MASLD development and progression.
methodsWe reviewed current literature on the role of PNPLA3 I148M in MASLD, focusing on gene-environment interactions involving diet, physical activity, obesity, and insulin resistance. We included studies analysing ethnic differences in PNPLA3 I148M prevalence and its association with MASLD. Additionally, we reviewed data on how PNPLA3 I148M influences the response to therapies, including lipid-lowering medications and GLP-1 agonists.
resultsThe PNPLA3 I148M variant markedly heightens MASLD risk, particularly in Hispanic populations, where a higher prevalence of MASLD is observed. Lifestyle factors such as high sugar intake, alcohol consumption, and physical inactivity exacerbate MASLD risk among I148M carriers. Evidence shows that insulin resistance amplifies MASLD risk associated with the I148M variant, especially in non-diabetic individuals. Moreover, the PNPLA3 I148M variant interacts with other genetic loci, further modifying MASLD risk and disease course. The variant also influences treatment response, with variability observed in effectiveness of lipid-lowering therapies and GLP-1 agonists among carriers.
conclusionThe interplay between PNPLA3 I148M and environmental factors underscores the need for personalized MASLD prevention and treatment strategies. Targeting both genetic and lifestyle contributors may enhance MASLD management, offering a tailored approach to reducing disease burden.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.