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Causal Relationship Between Varicose Veins and Mean Corpuscular Hemoglobin Concentration Based on Mendelian Randomization Study

Overview
Journal Thromb J
Publisher Biomed Central
Date 2024 Sep 3
PMID 39227935
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Abstract

Background: Increased hemoglobin concentrations may increase the risk of varicose veins. However, the underlying relationship between them was not yet understood.

Methods: 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.

Results: 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.

Conclusion: 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.

Citing Articles

The Roles of Oxidative Stress and Red Blood Cells in the Pathology of the Varicose Vein.

Gwozdzinski L, Pieniazek A, Gwozdzinski K Int J Mol Sci. 2025; 25(24.

PMID: 39769165 PMC: 11678264. DOI: 10.3390/ijms252413400.

References
1.
Li P, Wang H, Guo L, Gou X, Chen G, Lin D . Association between gut microbiota and preeclampsia-eclampsia: a two-sample Mendelian randomization study. BMC Med. 2022; 20(1):443. PMC: 9667679. DOI: 10.1186/s12916-022-02657-x. View

2.
Agarwal N, Gordeuk R, Prchal J . Genetic mechanisms underlying regulation of hemoglobin mass. Adv Exp Med Biol. 2008; 618:195-210. DOI: 10.1007/978-0-387-75434-5_15. View

3.
Ahti T, Makivaara L, Luukkaala T, Hakama M, Laurikka J . Effect of family history on the risk of varicose veins is affected by differential misclassification. J Clin Epidemiol. 2010; 63(6):686-90. DOI: 10.1016/j.jclinepi.2009.10.003. View

4.
Kaplan R, Criqui M, Denenberg J, Bergan J, Fronek A . Quality of life in patients with chronic venous disease: San Diego population study. J Vasc Surg. 2003; 37(5):1047-53. DOI: 10.1067/mva.2003.168. View

5.
Chen X, Hong X, Gao W, Luo S, Cai J, Liu G . Causal relationship between physical activity, leisure sedentary behaviors and COVID-19 risk: a Mendelian randomization study. J Transl Med. 2022; 20(1):216. PMC: 9100292. DOI: 10.1186/s12967-022-03407-6. View