Mediating Role of the ANGPTL3/TFPI Protein Ratio in Regulating T-Cell Surface Glycoprotein CD5 Levels on Knee Osteoarthritis (KOA): A Mendelian Randomization Study
Abstract
1. Introduction
2. Results
3. Discussion
3.1. The Impact of T-Cell Surface Glycoprotein CD5 Levels on KOA
3.1.1. The Total Effect (T-Cell Surface Glycoprotein CD5 Levels Were Negatively Correlated with KOA (β = −0.143))
3.1.2. The Mediating Effect of rQTL-ANGPTL3/TFPI
3.1.3. The Mediating Effect of rQTL-CPA1/CTRB1
3.1.4. The Mediating Effect of rQTL-HAGH/HBQ1
3.2. The Impact of C-X-C Motif Chemokine 9 Levels on KOA
3.2.1. The Total Effect (C-X-C Motif Chemokine 9 Levels Were Positively Correlated with KOA (β = 0.140))
3.2.2. The Mediating Effect of rQTL-MSRA/P4HB
3.2.3. The Mediating Effect of rQTL-COMP/DPP4
4. Methods and Materials
4.1. Data
4.1.1. Exposure Data
4.1.2. Mediator Data
4.1.3. Outcome Data
4.2. Statistics
4.2.1. MR Analysis
Forward MR Analysis
Reverse MR Analysis
4.2.2. Colocalization Analysis
4.2.3. False Discovery Rate Corrected (FDR-Corrected)
4.2.4. Mediation Analysis
5. Conclusions
Limitations
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Exposure | Outcome | SNPs | OR (95%CI) | PIVW | PHeterogeneity | PPleiotropy | Reverse MR PIVW |
---|---|---|---|---|---|---|---|
C-C motif chemokine 25 levels | KOA | 35 | 0.904 (0.843–0.969) | 0.004 | 0.387 | 0.288 | 0.557 |
T-cell surface glycoprotein CD5 levels | KOA | 31 | 0.867 (0.760–0.990) | 0.035 | 0.226 | 0.761 | 0.858 |
C-X-C motif chemokine 9 levels | KOA | 40 | 1.150 (1.001–1.320) | 0.048 | 0.128 | 0.506 | 0.346 |
Exposure | Outcome | SNPs | OR (95%CI) | PIVW |
---|---|---|---|---|
KOA | rQTL-CASP3/PDGFB | 4 | 1.061 (1.000–1.126) | 0.049 |
KOA | rQTL-CD40/TIMP3 | 3 | 1.161 (1.081–1.247) | 0.00004 |
KOA | rQTL-CEBPB/NADK | 4 | 1.068 (1.006–1.135) | 0.031 |
KOA | rQTL-DAG1/PDGFB | 4 | 1.069 (1.008–1.134) | 0.027 |
KOA | rQTL-EREG/TIMP3 | 3 | 1.129 (1.050–1.214) | 0.001 |
KOA | rQTL-F2R/PDGFB | 4 | 1.065 (1.004–1.130) | 0.037 |
KOA | rQTL-FXYD5/IRAK1 | 4 | 1.074 (1.012–1.140) | 0.019 |
KOA | rQTL-ITGB1/TFPI | 4 | 0.937 (0.884–0.992) | 0.026 |
KOA | rQTL-MVK/SERPINE1 | 4 | 1.063 (1.002–1.129) | 0.043 |
Exposure | Mediator | Outcome | Mediation Effect β1 | Mediation Effect β2 | Total Effect β | Mediated Proportion β1 × β2/β |
---|---|---|---|---|---|---|
T-cell surface glycoprotein CD5 levels | rQTL-ANGPTL3/TFPI | KOA | −0.084 | 0.159 | −0.143 | 9.340% |
rQTL-CPA1/CTRB1 | KOA | −0.178 | −0.095 | −0.143 | −11.825% | |
rQTL-HAGH/HBQ1 | KOA | 0.097 | 0.132 | −0.143 | −8.954% | |
C-X-C motif chemokine 9 levels | rQTL-COMP/DPP4 | KOA | −0.208 | 0.134 | 0.140 | −19.909% |
rQTL-MSRA/P4HB | KOA | −0.177 | −0.230 | 0.140 | 29.079% |
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Li, Y.; Liao, X.; Yu, X.; Xiao, Y.; Tao, X.; Zhong, T. Mediating Role of the ANGPTL3/TFPI Protein Ratio in Regulating T-Cell Surface Glycoprotein CD5 Levels on Knee Osteoarthritis (KOA): A Mendelian Randomization Study. Int. J. Mol. Sci. 2025, 26, 4471. https://doi.org/10.3390/ijms26104471
Li Y, Liao X, Yu X, Xiao Y, Tao X, Zhong T. Mediating Role of the ANGPTL3/TFPI Protein Ratio in Regulating T-Cell Surface Glycoprotein CD5 Levels on Knee Osteoarthritis (KOA): A Mendelian Randomization Study. International Journal of Molecular Sciences. 2025; 26(10):4471. https://doi.org/10.3390/ijms26104471
Chicago/Turabian StyleLi, Yongwei, Xi Liao, Xi Yu, Ying Xiao, Xiaoyu Tao, and Tian Zhong. 2025. "Mediating Role of the ANGPTL3/TFPI Protein Ratio in Regulating T-Cell Surface Glycoprotein CD5 Levels on Knee Osteoarthritis (KOA): A Mendelian Randomization Study" International Journal of Molecular Sciences 26, no. 10: 4471. https://doi.org/10.3390/ijms26104471
APA StyleLi, Y., Liao, X., Yu, X., Xiao, Y., Tao, X., & Zhong, T. (2025). Mediating Role of the ANGPTL3/TFPI Protein Ratio in Regulating T-Cell Surface Glycoprotein CD5 Levels on Knee Osteoarthritis (KOA): A Mendelian Randomization Study. International Journal of Molecular Sciences, 26(10), 4471. https://doi.org/10.3390/ijms26104471