Zhang Qi-Feng, Liu Qi-Li
Department of Andrology, Department of Urology, Guilin People's Hospital, Guilin, 541002, China.
Department of Vascular Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, China.
Sci Rep. 2025 Jun 4;15(1):19527. doi: 10.1038/s41598-025-03602-7.
Immune factors play a pivotal role in the development of vascular diseases. However, research on the relationship between immune cells and the risk of varicose veins remains limited. In this study, we utilized summary statistics from a genome-wide association study (GWAS) and employed bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between immune cell phenotypes and varicose veins. Sensitivity analyses were conducted to ensure the robustness of the results, including Cochran's Q test, MR Egger intercept test, leave-one-out analysis, and MR pleiotropy residual sum and outlier (MR-PRESSO) test. Additionally, results were subjected to false discovery rate (FDR) correction. Finally, Bayesian Weighted Mendelian Randomization (BWMR) was utilized to further validate the findings of the MR analysis. Our study identified significant causal associations between 5 immune cell phenotypes and the risk of varicose veins (FDR < 0.05). Specifically, CD86 on myeloid dendritic Cell and CD33 on CD33 + HLA DR + CD14dim show a significant positive causal relationship with the risk of varicose veins, while BAFF-R on IgD- CD24- B cell, BAFF-R on IgD + CD24- B cell, and BAFF-R on IgD + CD38- B cell exhibit a significant negative causal relationship with the risk of varicose veins. Additionally, when FDR was adjusted to 0.2, we found additional 7 immune cell phenotypes that are potentially associated with the risk of varicose veins. In particular, CD33 on CD33 + HLA DR+, CD33 on CD33 + HLA DR + CD14-, CD4 + T cell %T cell and CD39 + CD8 + T cell %CD8 + T cell are positively associated with the risk of varicose veins. In contrast, BAFF-R on B cell, BAFF-R on memory B cell and PDL-1 on CD14- CD16 + monocyte are negatively associated with the risk of varicose veins. The sensitivity analyses yielded results consistent with the main findings. Upon testing with the BWMR method, all results were consistent with those from the MR analysis, except for CD39 + CD8 + T cell %CD8 + T cell. Our study confirms a potential causal relationship between immune cells and varicose veins. This study provides new avenues to explore the mechanisms of varicose veins and lays the foundation for future investigations into targeted prevention strategies.
免疫因素在血管疾病的发展中起着关键作用。然而，关于免疫细胞与静脉曲张风险之间关系的研究仍然有限。在本研究中，我们利用全基因组关联研究（GWAS）的汇总统计数据，并采用双向双样本孟德尔随机化（MR）分析来研究免疫细胞表型与静脉曲张之间的因果关系。进行了敏感性分析以确保结果的稳健性，包括 Cochr an's Q检验、MR Egger截距检验、留一法分析和MR多效性残差和异常值（MR-PRESSO）检验。此外，对结果进行了错误发现率（FDR）校正。最后，利用贝叶斯加权孟德尔随机化（BWMR）进一步验证MR分析的结果。我们的研究确定了5种免疫细胞表型与静脉曲张风险之间存在显著的因果关联（FDR < 0.05）。具体而言，髓样树突状细胞上的CD86和CD33 + HLA DR + CD14dim上的CD33与静脉曲张风险呈显著正因果关系，而IgD-CD24-B细胞上的BAFF-R、IgD + CD24-B细胞上的BAFF-R和IgD + CD38-B细胞上的BAFF-R与静脉曲张风险呈显著负因果关系。此外，当将FDR调整至0.2时，我们发现另外7种免疫细胞表型可能与静脉曲张风险相关。特别是，CD33 + HLA DR+上的CD33、CD33 + HLA DR + CD14-上的CD33、CD4 + T细胞%T细胞和CD39 + CD8 + T细胞%CD8 + T细胞与静脉曲张风险呈正相关。相反，B细胞上的BAFF-R、记忆B细胞上的BAFF-R和CD14-CD16 + 单核细胞上的PDL-1与静脉曲张风险呈负相关。敏感性分析得出的结果与主要发现一致。在用BWMR方法进行检验时，除了CD39 + CD8 + T细胞%CD8 + T细胞外，所有结果均与MR分析的结果一致。我们的研究证实了免疫细胞与静脉曲张之间存在潜在的因果关系。本研究为探索静脉曲张的发病机制提供了新途径，并为未来针对性预防策略的研究奠定了基础。
