首页|PNPLA3 rs738409 C>G Variant Influences the Association Between Visceral Fat and Significant Fibrosis in Biopsy-proven Nonalcoholic Fatty Liver Disease

PNPLA3 rs738409 C>G Variant Influences the Association Between Visceral Fat and Significant Fibrosis in Biopsy-proven Nonalcoholic Fatty Liver Disease

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Background and Aims: Intra-abdominal visceral fat accu-mulation and patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 G/C gene polymorphism confer a greater susceptibility to nonalcoholic fatty liver disease (NAFLD). We examined whether the relationship between visceral fat ac-cumulation and liver disease severity may be influenced by PNPLA3 rs738409 polymorphism. Methods: The variant of PNPLA3 rs738409 was genotyped within 523 Han individu-als with biopsy-confirmed NAFLD. Visceral fat area (VFA) was measured by bioelectrical impedance. Significant liver fibrosis (SF), defined as stage F ≥2 on histology, was the outcome measure of interest. Results: The distribution of PNPLA3 genotypes was CC: 27.5％, CG: 48.2％, and GG: 24.3％. Higher VFA was associated with greater risk of hav-ing SF (adjusted-odds ratio [OR]: 1.03; 95％ confidence in-terval [CI]: 1.02–1.04, p<0.05), independent of potential confounders. Among subjects with the same VFA level, the risk of SF was greater among carriers of the rs738409 G genotype than among those who did not. Stratified analy-sis showed that PNPLA3 rs738409 significantly influenced the association between VFA and SF. VFA remained signifi-cantly associated with SF only among the rs738409 G-allele carriers (adjusted-OR: 1.05; 95％ CI: 1.03–1.08 for the GG group; and adjusted-OR:1.03; 95％ CI: 1.01–1.04 for the GC group). There was a significant interaction between VFA and PNPLA3 rs738409 genotype (Pinteraction=0.004). Con-clusions: PNPLA3 rs738409 G allele has a moderate effect on the association between VFA and risk of SF in adult indi-viduals with biopsy-proven NAFLD. Existence of the PNPLA3 rs738409 G allele and VFA interact to increase risk of SF.

Nonalcoholic fatty liver diseaseSignificant fibrosisVisceral fat areaSingle nucleotide polymorphismMetabolic dysfunction-associated fatty liver disease

Gang Li、Liang-Jie Tang、Pei-Wu Zhu、Ou-Yang Huang、Rafael S.Rios、Kenneth I.Zheng、Sui-Dan Chen、Hong-Lei Ma、Giovanni Targher、Christopher D.Byrne、Xiao-Yan Pan、Ming-Hua Zheng

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NAFLD Research Center,Department of Hepatology,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou,Zhejiang,China

Department of Laboratory Medicine,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou,Zhejiang,China

Department of Pathology,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou,Zhejiang,China

Section of Endocrinology,Diabetes and Metabolism,Department of Medicine,University and Azienda Ospedaliera Universitaria Integrata of Verona,Verona,Italy

Southampton National Institute for Health Research Biomedical Research Centre,University Hospital Southampton,Southampton General Hospital,Southampton,UK

Department of Endocrinology,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou,Zhejiang,China

Institute of Hepatology,Wenzhou Medical University,Wenzhou,Zhejiang,China

Key Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease in Zhejiang Province,Wenzhou,Zhejiang,China

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国家自然科学基金High Level Creative Talents from Department of Public Health in Zhe-jiang ProvinceProject of New Century 551 Talent Nurturing in WenzhouUniversity School of Medi-cine of Verona,Verona,ItalySouthampton NIHR Biomedical Research Centre UK

82070588S2032102600032IS-BRC-20004

2022

10.14218/JCTH.2021.00286

临床与转化肝病杂志(英文版)

临床与转化肝病杂志(英文版)

ISSN：
年,卷(期)：2022.10(3)
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