尿酸增加肝脏脂肪变性及非酒精性脂肪性肝病风险——基于NHANES及孟德尔随机化研究  

Increased uric acid and the risk of hepatic steatosis and non-alcoholic fatty liver disease based on NHANES and Mendelian randomization studies

作　　者：谭杰 曹玉萍 陈思 TAN Jie;CAO Yu-ping;CHEN Si(Department of Gastroenterology,First Affiliated Hospital of University of Science and Technology of China(Anhui Provincial Hospital),Hefei,Anhui 230001,China;不详)

机构地区：[1]中国科学技术大学附属第一医院(安徽省立医院)消化内科,安徽合肥230001 [2]安徽理工大学医学院

出　　处：《现代预防医学》2025年第3期418-423,共6页Modern Preventive Medicine

摘　　要：目的探讨尿酸与肝脏脂肪变性及非酒精性脂肪性肝病(NAFLD)风险之间的关系,为NAFLD的预防提供新思路。方法基于2017-2018年NHANES人群数据及全基因组关联研究汇总数据(GWAS),采用限制性立方样条模型、广义线性模型、二元logistic回归模型分析尿酸与肝脏脂肪变性及NAFLD风险的关联,运用逆方差加权法作为孟德尔随机化(MR)分析的主要方法,评估尿酸与NAFLD之间的因果关系,MR Egger回归法、加权中位数法、简单模型和加权模型对结果进行补充验证,随后进行敏感性检验。结果在调整所有协变量后,尿酸与肝脏脂肪变性及NAFLD风险均呈线性关系(Pnon-linear>0.05),且较高尿酸水平的人群,肝脏脂肪变性(β=3.559,95%CI:1.722~5.395,P<0.001)及NAFLD风险(OR=1.151,95%CI:1.048~1.265,P=0.003)更高。MR分析逆方差加权法显示,尿酸与NAFLD之间存在因果关系(OR=1.68,95%CI:1.01~2.81,P=0.049),其它四种分析方法提供相同方向的因果推断。敏感性检验提示工具变量间无明显异质性及水平多效性(P>0.05),且结果不受单个遗传变异的影响。结论尿酸与肝脏脂肪变性及NAFLD风险呈正线性相关,控制尿酸水平可能在预防和管理NAFLD中发挥重要作用。Objective To explore the relationship between uric acid and the risk of hepatic steatosis and non-alcoholic fatty liver disease(NAFLD),providing new insights for the prevention of NAFLD.Methods Utilizing data from the 2017-2018 NHANES population and summary data from genome-wide association studies(GWAS),the association between uric acid and the risk of hepatic steatosis and NAFLD was analyzed using restricted cubic spline models,generalized linear models,and binary logistic regression models.The inverse variance weighted method was employed as the primary approach for Mendelian randomization(MR)analysis to assess the causal relationship between uric acid and NAFLD.Additional verification of results was conducted using MR Egger regression,weighted median methods,simple models,and weighted models,followed by sensitivity testing.Results After adjusting for all covariates,a linear relationship was observed between uric acid and the risks of hepatic steatosis and NAFLD(Pnon-linear>0.05).Populations with higher uric acid levels exhibited increased risks of hepatic steatosis(β=3.559,95%CI:1.722-5.395,P<0.001)and NAFLD(OR=1.151,95%CI:1.048-1.265,P=0.003).The MR analysis using the inverse variance weighted method indicated a causal relationship between uric acid and NAFLD(OR=1.68,95%CI:1.01-2.81,P=0.049),with the other four analytical methods providing similar directional causal inferences.Sensitivity tests suggested no significant heterogeneity or horizontal pleiotropy among instrumental variables(P>0.05),and the results were not influenced by individual genetic variations.Conclusion Uric acid is positively linearly correlated with the risk of hepatic steatosis and NAFLD,indicating that controlling uric acid levels may play a crucial role in the prevention and management of NAFLD.

关 键 词：尿酸 非酒精性脂肪性肝病 NHANES 孟德尔随机化 因果推断 

分 类 号：R575.5[医药卫生—消化系统]