PNPLA3和SAMM50基因变异与亚洲人群的瘦型非酒精性脂肪性肝病相关。

PNPLA3 and SAMM50 variants are associated with lean nonalcoholic fatty liver disease in Asian population.

作者信息

Lu Chia-Wen, Chou Tzu-Jung, Wu Tsan-Yu, Lee Yi-Hsuan, Yang Hung-Jen, Huang Kuo-Chin

机构信息

Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Family Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.

Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Family Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu, Taiwan.

出版信息

Ann Hepatol. 2025 Jan-Jun;30(1):101761. doi: 10.1016/j.aohep.2024.101761. Epub 2024 Dec 3.

DOI:10.1016/j.aohep.2024.101761

PMID:39638042

Abstract

INTRODUCTION AND OBJECTIVES

Lean adults with nonalcoholic fatty liver disease (NAFLD) have a higher risk of metabolic syndrome than lean controls. The study aimed to investigate the clinical and genetic features of lean NAFLD which remain unclear in Asian populations.

MATERIALS AND METHODS

This was a genetic cohort study conducted in the HAVO Health Exam Clinic in 2020-2021 in Taiwan. Adults with a body mass index less than 24 kg/m were enrolled. Fatty liver was defined by ultrasonography. The candidate gene approach was based on the library of the NHGRI-EBI website. After removing duplication and nonsignificant variants, rs738409 in the PNPLA3 gene and rs3761472 in the SAMM50 gene were chosen. Multiple logistic regression models and receiver operating characteristic (ROC) curves were used.

RESULTS

A total of 1652 lean controls and 602 lean NAFLD patients were enrolled. The average age was 43.8 ± 11.5 years. Lean NAFLD subjects were older and had a higher percentage of metabolic syndrome (case vs. control: 10.5 % vs. 1.5 %). The GG genotypes of PNPLA3 rs12483959 (OR: 3.06; 95% CI: 2.15-4.37) and SAMM50 rs3761472 (OR: 2.90; 95% CI: 2.04-4.14) had a higher risk of fatty liver after adjusting for BMI and metabolic syndrome. The areas under the ROC curve for PNPLA3 rs738409 and SAMM50 rs3761472 in the detection of lean NAFLD were 0.859 (95%CI: 0.841, 0.877) and 0.860 (95%CI: 0.843, 0.877), respectively.

CONCLUSIONS

PNPLA3 rs738409 and SAMM50 rs3761472 gene polymorphisms are associated with a higher risk of fatty liver in lean individuals independent of BMI and metabolic syndrome in Asian populations.

摘要

引言与目的

非酒精性脂肪性肝病（NAFLD）的瘦成年人患代谢综合征的风险高于瘦对照组。本研究旨在调查亚洲人群中尚不清楚的瘦型NAFLD的临床和遗传特征。

材料与方法

这是一项于2020 - 2021年在台湾HAVO健康检查诊所进行的基因队列研究。纳入体重指数小于24kg/m²的成年人。通过超声检查定义脂肪肝。候选基因方法基于NHGRI - EBI网站的文库。在去除重复和无意义的变异后，选择了PNPLA3基因中的rs738409和SAMM50基因中的rs3761472。使用了多元逻辑回归模型和受试者工作特征（ROC）曲线。

结果

共纳入1652名瘦对照组和602名瘦型NAFLD患者。平均年龄为43.8±11.5岁。瘦型NAFLD受试者年龄更大，代谢综合征的百分比更高（病例组与对照组：10.5%对1.5%）。在调整BMI和代谢综合征后，PNPLA3 rs12483959的GG基因型（OR：3.06；95%CI：2.15 - 4.37）和SAMM50 rs3761472的GG基因型（OR：2.90；95%CI：2.04 - 4.14）患脂肪肝的风险更高。PNPLA3 rs738409和SAMM50 rs3761472在检测瘦型NAFLD时的ROC曲线下面积分别为0.859（95%CI：0.841，0.877）和0.860（95%CI：0.843，0.877）。