Evidence map›Paper›PMID 25964223›Full record

SynthesisThe American journal of gastroenterology2015

PNPLA3 Gene Polymorphism Is Associated With Predisposition to and Severity of Alcoholic Liver Disease.

Habeeb Salameh, Evan Raff, Angelika Erwin, Devanshi Seth, Hans Dieter Nischalke, Edmondo Falleti, Maria Antonella Burza, Julian Leathert, Stefano Romeo, Antonio Molinaro and 8 more

Erratum issuedOpen access · greenAbstract readMeta-AnalysisSystematic Review
PubMed Publisher
In one paragraph

Synthesis in The American journal of gastroenterology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 76 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed, 4 pooled it
10.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

76 citing papers in PubMed, 4 syntheses or guidelines pooled it, 153 citations in OpenAlex.

  1. Pooled it
  2. ACG Clinical Guideline: Alcoholic Liver Disease.The American journal of gastroenterology · 2018
    Guideline
  3. Pooled it
  4. Diagnosis and Treatment of Alcoholic Hepatitis: A Systematic Review.Alcoholism, clinical and experimental research · 2016
    Pooled it
  5. Precision pathophysiology in steatotic liver disease.Clinical and molecular hepatology · 2026
    Review
  6. Review
  7. Article
  8. Review
  9. Gene-based therapies for steatotic liver disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  10. Non-coding RNAs in alcohol-associated liver disease.Liver research (Beijing, China) · 2025
    Review
  11. Experimental Models to Investigate PNPLA3 in Liver Steatosis.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Review
  12. Article
  13. Acute alcohol-associated hepatitis: Latest findings in non-invasive biomarkers and treatment.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Review
  14. Review
  15. Alcohol and Hepatocellular Carcinoma.Clinics in liver disease · 2024
    Review
  16. Review
  17. Review
  18. A study of genetic variants, genetic risk score and DNA methylation of PNPLA3 and TM6SF2 in alcohol liver cirrhosis.Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology · 2023
    Article
  19. Review
  20. Review

16 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 8 institutions in 6 countries.

Habeeb SalamehDepartment of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, USA.
Evan RaffDepartment of Internal Medicine, University of Alabama, Birmingham, Alabama, USA.
Angelika ErwinGenomic Medicine Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Devanshi Seth1] Drug Health Services, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia [2] Centenary Institute of Cancer Medicine and Cell Biology, Camperdown, New South Wales, Australia [3] Faculty of Medicine, University of Sydney, Sydney, New South Wales, Australia.
Hans Dieter NischalkeDepartment of Internal Medicine, University of Bonn, Bonn, Germany.
Edmondo FalletiLaboratory Medicine-Istituto Patologia Clinica, Azienda Ospedaliero Universitaria, Udine, Italy.
Maria Antonella BurzaInstitute of Medicine, Department of Molecular and Clinical Medicine, Wallenberg Laboratory, University of Gothenburg, Gothenburg, Sweden.
Julian LeathertInstitute of Cellular Medicine, Newcastle University Medical School, Newcastle upon Tyne, UK.
Stefano Romeo1] Institute of Medicine, Department of Molecular and Clinical Medicine, Wallenberg Laboratory, University of Gothenburg, Gothenburg, Sweden [2] Department of Medical and Surgical Science, University Magna Grecia of Catanzaro, Clinical Nutrition Unit, Germaneto, Catanzaro, Italy.
Antonio MolinaroInstitute of Medicine, Department of Molecular and Clinical Medicine, Wallenberg Laboratory, University of Gothenburg, Gothenburg, Sweden.
Stefano Ginanni CorradiniDepartment of Clinical Medicine, Division of Gastroenterology, Sapienza University of Rome, Rome, Italy.
Pierluigi ToniuttoDepartment of Medical Sciences Experimental and Clinical, Medical Liver Transplantation Unit, University of Udine, Udine, Italy.
Ulrich Spengler
Spengler UlrichDepartment of Internal Medicine, University of Bonn, Bonn, Germany.
Ann DalyFaculty of Medical Sciences, Newcastle University Medical School, Newcastle upon Tyne, UK.
Christopher P DayFaculty of Medical Sciences, Newcastle University Medical School, Newcastle upon Tyne, UK.
Yong-Fang KuoDepartment of Biostatistics, University of Texas Medical Branch, Galveston, Texas, USA.
Ashwani K SingalDivision of Gastroenterology and Hepatology, University of Alabama, Birmingham, Alabama, USA.
The University of Texas Medical Branch at Galveston · USUniversity of Gothenburg · SEUniversity of Alabama at Birmingham · USUniversity of Bonn · DECentenary Institute · AUCleveland Clinic · USNewcastle University · GBUniversity of Udine · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesThe genetic polymorphism with an isoleucine-to-methionine substitution at position 148 (rs738409 C>G) in the patatin-like phospholipase domain protein 3 (PNPLA3) gene confers risk of steatosis. PNPLA3 polymorphism is shown to be associated with alcoholic liver disease (ALD). We performed a systematic review and meta-analysis to examine association of this genetic polymorphism with ALD spectrum and its severity.

methodsMedline, Embase, and Cochrane Library were searched for studies on association of PNPLA3 polymorphism and ALD spectrum: alcoholic fatty liver (AFL), alcoholic liver injury (ALI), alcoholic cirrhosis (AC), and hepatocellular carcinoma (HCC). Pooled data are reported as odds ratio (OR) with 95% confidence interval. Heterogeneity was assessed using the I(2) statistics and publication bias using Egger's test and Begg and Mazumdar's test. Individual participant data obtained from five studies were used for subgroup analyses.

resultsAmong 10 studies included in this pooled analysis, compared with controls, OR for rs738409 CG and GG among ALI patients was 1.45 (1.24-1.69) and 2.22 (1.50-3.28), respectively, compared with CC. Respective OR among AC patients was 2.09 (1.79-2.44) and 3.37 (2.49-4.58) and among AC patients with HCC was 2.87 (1.61-5.10) and 12.41 (6.99-22.03). Data for AFL were inconsistent. Among ALD patients, OR of CG and GG genotypes was 2.62 (1.73-3.97) and 8.45 (2.52-28.37), respectively, for AC compared with fatty liver (FL) patients. Similar OR for AC compared with ALI was 1.98 (1.24-3.17) and 3.86 (1.18-12.60). The OR for CG and GG genotypes among AC patients for HCC occurrence was 1.43 (0.76-2.72) and 2.81 (1.57-5.01), respectively. Individual participant data analysis showed age to predispose to AC among ALI patients.

conclusionsPNPLA3 genetic polymorphism (rs738409 C>G) is associated with increased risk for the entire spectrum of ALD among drinkers including ALI, AC, and HCC. Studies are needed to clarify association of PNPLA3 polymorphism and steatosis in alcoholics. PNPLA3 gene may potentially be a therapeutic target in ALD.

Indexed as

AcyltransferasesCarcinoma, HepatocellularCentral Nervous System DepressantsChemical and Drug Induced Liver InjuryEthanolFatty Liver, AlcoholicGenetic Predisposition to DiseaseHumansLipaseLiver Cirrhosis, AlcoholicLiver Diseases, AlcoholicLiver NeoplasmsMembrane ProteinsPhospholipases A2, Calcium-IndependentPolymorphism, Single NucleotideSeverity of Illness IndexAcyltransferasesCentral Nervous System DepressantsEthanolLipaseMembrane ProteinsPhospholipases A2, Calcium-IndependentPNPLA3 protein, human

Identifiers

PMID25964223
OpenAlexW2116867710

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.