ArticlePloS one2015
The Impact of PNPLA3 rs738409 Genetic Polymorphism and Weight Gain ≥10 kg after Age 20 on Non-Alcoholic Fatty Liver Disease in Non-Obese Japanese Individuals.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- AGA Clinical Practice Update: Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Lean Individuals: Expert Review.Gastroenterology · 2022Guideline
- Trial
- Burden and Health System Challenges in MASLD Across East and Southeast Asia: A Narrative Review.Health science reports · 2026Review
- Genetic variants influencing liver fat in normal-weight individuals of European ancestry.JHEP reports : innovation in hepatology · 2025Article
- Risk of hepatocellular carcinoma according to body mass index and waist circumference in nonalcoholic fatty liver disease.World journal of gastrointestinal oncology · 2025Article
- Article
- PNPLA3 I148M Interacts With Environmental Triggers to Cause Human Disease.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- A 4-year cohort study of the effects of PNPLA3 rs738409 genotypes on liver fat and fibrosis and gut microbiota in a non-fatty liver population.Environmental health and preventive medicine · 2025Article
- The global landscape of lean metabolic dysfunction-associated steatotic liver disease: insight from Asia and the West.Frontiers in gastroenterology (Lausanne, Switzerland) · 2025Review
- Metabolic dysfunction associated fatty liver disease in healthy weight individuals.Hepatology international · 2024Review
- Article
- Prognosis of biopsy-confirmed metabolic dysfunction- associated steatotic liver disease: A sub-analysis of the CLIONE study.Clinical and molecular hepatology · 2024Article
- Lifestyle interventions in nonalcoholic fatty liver disease.Nature reviews. Gastroenterology & hepatology · 2023Review
- Survey of Dietary Habits and Physical Activity in Japanese Patients with Non-Obese Non-Alcoholic Fatty Liver Disease.Nutrients · 2023Article
- The FIB-4 Index Predicts the Development of Liver-Related Events, Extrahepatic Cancers, and Coronary Vascular Disease in Patients with NAFLD.Nutrients · 2022Article
- Article
- Association of Low Skeletal Muscle Mass with the Phenotype of Lean Non-Alcoholic Fatty Liver Disease.Healthcare (Basel, Switzerland) · 2022Article
- The Risk of Cirrhosis and Its Complications Based on PNPLA3 rs738409 G Allele Frequency.Digestive diseases (Basel, Switzerland) · 2022Article
- Clinical practice advice on lifestyle modification in the management of nonalcoholic fatty liver disease in Japan: an expert review.Journal of gastroenterology · 2021Review
- Nonalcoholic fatty liver disease (NAFLD) from pathogenesis to treatment concepts in humans.Molecular metabolism · 2021Review
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Non-alcoholic fatty liver disease (NAFLD) in non-obese individuals is inadequately elucidated. We aim to investigate the impact of known genetic polymorphisms on NAFLD and the interaction between genetic risks and weight gain on NAFLD in obese and non-obese Japanese individuals. A total of 1164 participants who received health checkups were included. Participants with excessive alcohol consumption, with viral hepatitis or other inappropriate cases were excluded. Fatty liver was diagnosed by ultrasonography. Participants with a body mass index (BMI) of <18.5 kg/m2, 18.5-22.9 kg/m2, 23.0-24.9 kg/m2 and ≥25 kg/m2 were classified underweight, normal weight, overweight and obese, respectively. Self-administered questionnaire for lifestyle was assessed and a total of 8 previously reported genetic polymorphisms were chosen and examined. In all, 824 subjects were enrolled. The overall prevalence of NAFLD was 33.0%: 0% in underweight, 15.3% in normal weight, 41.1% in overweight and 71.7% in obese individuals. The prevalence of NAFLD is more affected by the G allele of patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 in normal weight (odds ratio (OR) 3.52; 95%-CI: 1.42-8.71; P = 0.0063) and in overweight individuals (OR 2.60; 95%-CI: 1.14-5.91; P = 0.0225) than in obese individuals (not significant). Moreover, the G allele of PNPLA3 rs738409 and weight gain ≥10 kg after age 20 had a joint effect on the risk of NAFLD in the normal weight (OR 12.00; 95% CI: 3.71-38.79; P = 3.3×10-5) and the overweight individuals (OR 13.40; 95% CI: 2.92-61.36; P = 0.0008). The G allele of PNPLA3 rs738409 is a prominent risk factor for NAFLD and the interaction between the PNPLA3 rs738409 and weight gain ≥10 kg after age 20 plays a crucial role in the pathogenesis of NAFLD, especially in non-obese Japanese individuals.
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