基于孟德尔随机化探究尿酸盐与肾功能损伤风险的因果关系  

Investigating the causal relationship between urate and the risk of renal function impairment by mendelian randomization

作　　者：孙天杰 王沁 何丽君 李婷婷 SUN Tianjie;WANG Qin;HE Lijun;LI Tingting(University of Shanghai for Science and Technology,Shanghai 200093;Shanghai University of Medicine&Health Sciences,Shanghai 201318)

机构地区：[1]上海理工大学健康科学与工程学院,上海200093 [2]上海健康医学院医学技术学院,上海201318

出　　处：《北京生物医学工程》2025年第1期32-38,共7页Beijing Biomedical Engineering

基　　金：上海市科委“青年科技英才扬帆”计划项目(21YF1418900)资助。

摘　　要：目的基于孟德尔随机化探究尿酸盐和肾功能损伤,包括肾小球滤过率功能下降、血清尿素氮水平异常以及尿白蛋白/肌酐比值升高之间的直接因果关系。方法以尿酸盐与肾功能损伤疾病相关的全基因组关联数据为基础,寻找出两种性状之间单核核苷酸多态性位点,并且设置参数P<5×10^(-8),连锁不平衡参数r^(2)=0.001,遗传区域宽度为10000 kb,运用5种孟德尔随机化方法包括逆方差加权法、MR-Egger回归法、加权中位数法、基于众数的简单估计和基于众数的加权估计进行孟德尔随机化分析,并且通过异质性检验、水平多效性检验、逐个剔除敏感性检验进行验证和分析。结果去除混杂因素后共筛选出78个与尿酸盐相关的工具变量。逆方差加权结果显示尿酸盐与肾小球滤过率功能下降之间具有因果关系(OR=0.971,95%CI=0.954~0.988),机体内尿酸盐水平升高,肾小球滤过率功能降低。尿酸盐与血清尿素氮水平异常无因果关系(OR=1.025,95%CI=1.011~1.040),与尿白蛋白/肌酐比值升高无因果关系(OR=1.000,95%CI=0.968~1.034)。结论利用孟德尔随机化排除混杂因素后,得到的结果可以发现尿酸盐与肾小球滤过率功能具有因果关系并呈负相关,尿酸盐与血清尿素氮水平异常和尿白蛋白/肌酐比值升高具有临床关联性但无因果关系。本文结果为肾功能损伤的早期筛查和延缓该疾病的发展,改善患者长期预后有具有重要意义。Objective A causal relationship between Urate and renal impairment including decreased glomerular filtration rate function,abnormal serum urea nitrogen levels,and elevated urinary albumin/creatinine ratio is investigated based on Mendelian randomization.Methods Based on the Genome-wide association data of urate and renal function impairment diseases,the mononucleotide polymorphism loci between the two traits were found,and the parameters P<5×10^(-8),linkage imbalance r^(2)=0.001,and genetic region width of 10000 kb were set.Five Mendelian randomization methods,including inverse variance weighting method,MR-Egger regression method,weighted median method,simple model-based estimation and model-based weighted estimation,were used to conduct Mendelian randomization analysis,and were verified and analyzed by heterogeneity test,horizontal pleotropy test and one by one elimination sensitivity test.Results After removing confounding factors,78 instrumental variables related to urate were selected.Inverse variance weighted results showed that there was a causal relationship between urate and glomerular filtration rate(OR=0.971,95%CI=0.954-0.988).As urate level increased in the body,glomerular filtration rate function decreased.There was no causal relationship between urate and blood urea nitrogen levels(OR=1.025,95%CI=1.011-1.040),and no causal relationship between urate and increased urinary albumin/creatinine ratio(OR=1.000,95%CI=0.968-1.034).Conclusions Using Mendelian randomization to exclude confounding factors,the results showed that urate was causally and negatively correlated with the function of glomerular filtration rate,and that urate was clinically associated with blood urea nitrogen levels and elevated urinary albumin/creatinine ratio,but not causally.The results of this study are of great significance for early screening of renal injury,delaying the development of the disease and improving the long-term prognosis of patients.

关 键 词：孟德尔随机化 肾功能损伤 尿酸盐 高尿酸血症 

分 类 号：R318.04[医药卫生—生物医学工程]