Evidence map›Paper›PMID 40074353›Full record

ArticleEnvironmental health and preventive medicine2025

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.

Satoshi Sato, Chikara Iino, Takafumi Sasada, Keisuke Furusawa, Kenta Yoshida, Kaori Sawada, Tatsuya Mikami, Shinsaku Fukuda, Shigeyuki Nakaji, Hirotake Sakuraba

Abstract read
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Article in Environmental health and preventive medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

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3citing papers in PubMed
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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
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  3. Journal of clinical and experimental hepatology
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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Satoshi SatoDepartment of Gastroenterology, Hematology and Clinical Immunology, Hirosaki University Graduate School of Medicine.ORCID http://orcid.org/0000-0001-5569-7093
Chikara IinoDepartment of Gastroenterology, Hematology and Clinical Immunology, Hirosaki University Graduate School of Medicine.
Takafumi SasadaDepartment of Gastroenterology, Hematology and Clinical Immunology, Hirosaki University Graduate School of Medicine.
Keisuke FurusawaDepartment of Gastroenterology, Hematology and Clinical Immunology, Hirosaki University Graduate School of Medicine.
Kenta YoshidaDepartment of Gastroenterology, Hematology and Clinical Immunology, Hirosaki University Graduate School of Medicine.
Kaori SawadaDepartment of Preemptive Medicine, Hirosaki University Graduate School of Medicine.
Tatsuya MikamiDepartment of Preemptive Medicine, Hirosaki University Graduate School of Medicine.
Shinsaku FukudaDepartment of Preemptive Medicine, Hirosaki University Graduate School of Medicine.
Shigeyuki NakajiDepartment of Preemptive Medicine, Hirosaki University Graduate School of Medicine.
Hirotake SakurabaDepartment of Gastroenterology, Hematology and Clinical Immunology, Hirosaki University Graduate School of Medicine.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMany factors are associated with the development and progression of liver fat and fibrosis; however, genetics and the gut microbiota are representative factors. Moreover, recent studies have indicated a link between host genes and the gut microbiota. This study investigated the effect of patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 (C > G), which has been reported to be most involved in the onset and progression of fatty liver, on liver fat and fibrosis in a cohort study related to gut microbiota in a non-fatty liver population.

methodsThis cohort study included 214 participants from the health check-up project in 2018 and 2022 who had non-fatty liver with controlled attenuation parameter (CAP) values <248 dB/m by FibroScan and were non-drinkers. Changes in CAP values and liver stiffness measurement (LSM), liver-related items, and gut microbiota from 2018 to 2022 were investigated separately for PNPLA3 rs738409 CC, CG, and GG genotypes.

resultsBaseline values showed no difference among the PNPLA3 rs738409 genotypes for any of the measurement items. From 2018 to 2022, the PNPLA3 rs738409 CG and GG genotype groups showed a significant increase in CAP and body mass index; no significant change was observed in the CC genotype group. LSM increased in all genotypes, but the rate of increase was highest in the GG genotype, followed by the CG and CC genotypes. Fasting blood glucose levels increased in all genotypes; however, HOMA-IR (Homeostasis Model Assessment of Insulin Resistance) increased significantly only in the GG genotype. HDL (high-density lipoprotein) and LDL (low-density lipoprotein) cholesterol levels significantly increased in all genotypes, whereas triglycerides did not show any significant changes in any genotype. As for the gut microbiota, the relative abundance of Feacalibacterium in the PNPLA3 rs738409 GG genotype decreased by 2% over 4 years, more than 2-fold compared to CC and GG genotypes. Blautia increased significantly in the CC group.

conclusionThe results suggest that PNPLA3 G-allele carriers of non-fatty liver develop liver fat and fibrosis due to not only obesity and insulin resistance but also the deterioration of gut microbiota, which may require a relatively long course of time, even years.

Indexed as

Gastrointestinal MicrobiomeLipaseLiver CirrhosisMembrane ProteinsNon-alcoholic Fatty Liver DiseaseAcyltransferasesAdultCohort StudiesFemaleGenotypeHumansMaleMiddle AgedPhospholipases A2, Calcium-IndependentPolymorphism, Single NucleotideAcyltransferasesLipaseMembrane ProteinsPhospholipases A2, Calcium-IndependentPNPLA3 protein, humanCohort studyGut microbiotaLiver fatLiver fibrosisPatatin-like phospholipase domain-containing 3 (PNPLA3)

Identifiers

PMID40074353
PMCPMC11925709

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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.