Chen Shiwei, Zhou Huandong, Liu Shicheng, Meng Luyang
The Third People's Hospital of Hangzhou, Zhejiang Province, 310009, China.
Thromb J. 2024 Sep 3;22(1):79. doi: 10.1186/s12959-024-00647-y.
Increased hemoglobin concentrations may increase the risk of varicose veins. However, the underlying relationship between them was not yet understood.
Mendelian randomization (MR) analysis was performed to investigate causal effect between mean corpuscular hemoglobin concentration (MCHC, exposure factor) and varicose veins (outcome). Afterward, sensitivity analysis was used to ensure the reliability of MR analysis results. Then Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of SNPs were performed. A search tool for recurring instances of neighbouring genes (STRING) database was used to construct a protein-protein interaction (PPI) network.
Therefore, the inverse-variance weighted (IVW) results showed there existed a causal relationship between MCHC and varicose veins (p = 0.0026), with MCHC serving as a significant risk factor. (odd ratio [OR] = 1.2321). In addition, the validity of the results of the forward MR analysis was verified by sensitivity analysis. Further, a PPI network of 92 single-nucleotide polymorphisms (SNPs) which used for forward MR analysis related genes was constructed. And they were found to be closely associated with the peroxisome proliferator-activated receptor (PPAR) signalling pathway and cellular response to external stimulus by enrichment analysis. In addition, we clarified that the effect of varicose veins on MCHC was minimal by reverse MR analysis, suggesting that the results of forward MR analysis were not disturbed by reverse results.
This study found a causal relationship between varicose veins and MCHC, which provided strong evidence for the effect of hemoglobin on varicose veins, and a new thought for the diagnosis and prevention of varicose veins in the future.
血红蛋白浓度升高可能会增加静脉曲张的风险。然而，它们之间的潜在关系尚不清楚。
进行孟德尔随机化（MR）分析，以研究平均红细胞血红蛋白浓度（MCHC，暴露因素）与静脉曲张（结局）之间的因果效应。随后，进行敏感性分析以确保MR分析结果的可靠性。然后对单核苷酸多态性（SNP）进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析。使用相邻基因重复实例搜索工具（STRING）数据库构建蛋白质-蛋白质相互作用（PPI）网络。
因此，逆方差加权（IVW）结果显示MCHC与静脉曲张之间存在因果关系（p = 0.0026），MCHC是一个显著的危险因素。（比值比[OR]=1.2321）。此外，通过敏感性分析验证了正向MR分析结果的有效性。进一步构建了用于正向MR分析相关基因的92个单核苷酸多态性（SNP）的PPI网络。通过富集分析发现它们与过氧化物酶体增殖物激活受体（PPAR）信号通路和细胞对外界刺激的反应密切相关。此外，我们通过反向MR分析阐明了静脉曲张对MCHC的影响最小，这表明正向MR分析的结果不受反向结果的干扰。
本研究发现静脉曲张与MCHC之间存在因果关系，为血红蛋白对静脉曲张的影响提供了有力证据，并为未来静脉曲张的诊断和预防提供了新思路。
