血清尿酸水平与脑血管病因果关系的双向两样本孟德尔随机化研究  

Causal relationship between serum uric acid leveland cerebrovascular disease: a two-samplebidirectional Mendelian randomization study

作　　者：韩秀燕 许华 张沁丽[1] HAN Xiuyan;XU Hua;ZHANG Qinli(Department of Neurology,Heping Hospital Affiliated to Changzhi Medical College,Changzhi,Shanxi,046000;Graduate School,Changzhi Medical College,Changzhi,Shanxi,046000)

机构地区：[1]长治医学院附属和平医院神经内科,山西长治046000 [2]长治医学院研究生院,山西长治046000

出　　处：《实用临床医药杂志》2025年第1期66-72,共7页Journal of Clinical Medicine in Practice

基　　金：山西省卫生计生委科研课题计划项目(2017164)。

摘　　要：目的 采用两样本双向孟德尔随机化(MR)研究评估血清尿酸(SUA)水平与脑血管病(CVD)的因果关联。方法 从全基因组关联研究(GWAS)中获取两样本的单核苷酸多态性(SNPs)作为工具变量。以逆方差加权法(IVW)为主要方法,以加权中位数法、加权模式方法和MR-Egger回归作为补充,进行敏感性分析以验证结果的稳健性。结果 正向IVW分析结果显示,SUA升高是中风(OR=1.183, 95%CI:1.081~1.295,P=2.51×10^(-4))、缺血性卒中(OR=1.196, 95%CI:1.084~1.320,P=3.81×10^(-4))、大动脉粥样硬化性卒中(OR=1.466, 95%CI:1.134~1.897,P=0.004)的危险因素,是血管性痴呆(OR=0.451, 95%CI:0.273~0.745,P=0.002)、多发梗死性痴呆(OR=0.372, 95%CI:0.144~0.959,P=0.041)的保护因素。反向IVW分析结果则不支持基因预测的CVD风险对SUA水平存在因果影响。所有显著性结果均经Bonferroni校正P<0.005。敏感性分析进一步证实了本研究结果的可靠性。结论 MR分析显示,SUA水平升高与中风、缺血性卒中、大动脉粥样硬化性卒中的发病风险呈正相关,与血管性痴呆、多发梗死性痴呆的发病风险呈负相关。Objective To evaluate the causal relationship between serum uric acid(SUA)level and cerebrovascular disease(CVD)by a two-sample bidirectional Mendelian randomization(MR)study.Methods Single nucleotide polymorphisms(SNPs)from Genome-Wide Association Studies(GWAS)were obtained as instrumental variables for both samples.Inverse-variance weighted(IVW)method was primarily adopted,with weighted median method,weighted mode method,and MR-Egger regression serving as supplementary approaches for sensitivity analyses to verify the robustness of the results.Results The forward IVW analysis results showed that increased SUA was a risk factor for stroke(OR=1.183,95%CI,1.081 to 1.295,P=2.51×10^(-4)),ischemic stroke(OR=1.196,95%CI,1.084 to 1.320,P=3.81×10^(-4)),and large artery atherosclerotic stroke(OR=1.466,95%CI,1.134 to 1.897,P=0.004),and also a protective factor for vascular dementia(OR=0.451,95%CI,0.273 to 0.745,P=0.002)and multi-infarct dementia(OR=0.372,95%CI,0.144 to 0.959,P=0.041).The reverse IVW analysis results did not support a causal effect of genetically predicted CVD risk on SUA level.All significant results were corrected by Bonferroni with P value less than 0.005.Sensitivity analyses further confirmed the reliability of the study findings.Conclusion The MR analysis reveals positive correlations between increased SUA level and the risk of stroke, ischemic stroke and large artery atherosclerotic stroke , and negative correlations ofSUA level with the risk of vascular dementia and multi-infarct dementia.

关 键 词：血清尿酸 脑血管病 孟德尔随机化分析 双向因果关联 全基因组关联研究 

分 类 号：R743.3[医药卫生—神经病学与精神病学] R394[医药卫生—临床医学] R319