Liu Yue, Li Shiwei, Zhang Xinxin, Huang Bo, Fu Yuhong, Li Xin, Cui Jingqiu
Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China.
Department of Nephropathy, Tianjin Medical University General Hospital, Tianjin, China.
Nutr Metab Cardiovasc Dis. 2024 Apr;34(4):1021-1027. doi: 10.1016/j.numecd.2024.01.018. Epub 2024 Jan 17.
Previous experimental and observational studies showed that serum uric acid (SUA) was associated with deep venous thrombosis (DVT), but the causal relationship is unclear. This study aimed to explore the potential causal association between SUA and DVT.
We designed a two-sample Mendelian randomization (MR) analysis by using summary-level data from large genome-wide association studies performed in European individuals. A total of 14 SUA-related single-nucleotide polymorphisms (SNPs) (P value < 5 × 10-8) were identified as instrumental variables. The inverse variance weighted method was used as the primary method to compute the odds ratios (ORs) and 95 % confidence intervals (95 % CIs) for per standard deviation increase in SUA. MR Egger, weighted median, weighted mode, and simple mode were also applied to test the robustness of the results. We found no significant causal effects of serum uric acid on deep venous thrombosis (odds ratio [OR]: 1.000, 95 % confidence interval [CI]: 0.998-1.002, p = 0.78) by using inverse variance weighted. MR analyses based on other methods showed similar results.
There was no potential causal associations between higher genetically predicted SUA levels and increased risk of deep venous thrombosis. Further, MR studies with more valid SNPs and more DVT cases are needed. Validation of the findings is also recommended.
既往的实验和观察性研究表明,血清尿酸(SUA)与深静脉血栓形成(DVT)有关,但因果关系尚不清楚。本研究旨在探讨SUA与DVT之间潜在的因果关联。
我们利用在欧洲人群中进行的大型全基因组关联研究的汇总数据,设计了一项两样本孟德尔随机化(MR)分析。共鉴定出14个与SUA相关的单核苷酸多态性(SNP)(P值<5×10-8)作为工具变量。采用逆方差加权法作为主要方法,计算SUA每增加一个标准差的比值比(OR)和95%置信区间(95%CI)。还应用MR Egger、加权中位数、加权众数和简单众数来检验结果的稳健性。采用逆方差加权法,我们发现血清尿酸对深静脉血栓形成无显著因果效应(比值比[OR]:1.000,95%置信区间[CI]:0.998-1.002,p=0.78)。基于其他方法的MR分析显示了相似的结果。
较高的遗传预测SUA水平与深静脉血栓形成风险增加之间不存在潜在的因果关联。此外,需要进行更多有效SNP和更多DVT病例的MR研究。还建议对研究结果进行验证。