Sun Lin, Yan Kai-Qing, Zhang Qi, Ma Ji, Shi Bo, Yang Xi-Yuan, Li Li-Jun
The Fifth Affiliated Hospital Shanxi Medical University Taiyuan People's Republic of China.
The Second Affiliated Hospital Shanxi Medical University Taiyuan People's Republic of China.
JOR Spine. 2025 Jan 7;8(1):e70034. doi: 10.1002/jsp2.70034. eCollection 2025 Mar.
Several matrix metalloproteinases (MMPs) have been reported to be associated with intervertebral disc degeneration (IDD) in several previous studies. However, the causal relationship between MMPs and IDD remains unclear. In this study, Mendelian randomization (MR) was used to analyze the causal relationship between the plasma levels of multiple MMPs and the risk of IDD.
The GWAS data of the plasma levels of MMP1, MMP3, MMP7, MMP10, and MMP12 were derived from the genome-wide variation associations of 21 758 European individuals. The genetic associations of the variants with IDD were investigated in the largest genome-wide association study from GWAS pipeline using Phesant derived variables from UKBiobank (1045 cases; 461 965 controls). We used a two-sample MR method to evaluate the causal relationship between these five MMPs and IDD. The causal effects were examined by inverse variance weighted (IVW) test. And sensitivity analysis was performed using Q test of IVW and MR-Egger, MR-Egger-intercept and MR-PRESSO.
We found a significant correlation between increased the plasma level of MMP3 and an increased risk of IDD (IVW: OR 1.000564, 95% CI 1.0000304-1.00110; = 0.0383). The heterogeneity test (MR-Egger Q test: = 0.346 and IVW Q test: = 0.460) indicated that there was no heterogeneity in this instrumental variable on the surface. Also, no directional horizontal pleiotropy was observed in the MR analysis (MR-Egger, = 0.708 and MR-PRESSO, = 0.609). There was no significant correlation between the plasma levels of MMP1, MMP7, MMP10, and MMP12 and an increased risk of IDD.
Our MR analysis found that there is a potential causal relationship between increased the plasma level of MMP3 and the risk of IDD in the European population. There is no potential causal relationship between the plasma levels of MMP1, MMP7, MMP10, and MMP12 and an increased risk of IDD.
在先前的多项研究中，已有报道称几种基质金属蛋白酶（MMPs）与椎间盘退变（IDD）相关。然而，MMPs与IDD之间的因果关系仍不明确。在本研究中，采用孟德尔随机化（MR）分析多种MMPs血浆水平与IDD风险之间的因果关系。
MMP1、MMP3、MMP7、MMP10和MMP12血浆水平的全基因组关联研究（GWAS）数据来自21758名欧洲个体的全基因组变异关联。使用来自英国生物银行（1045例；461965例对照）的Phesant衍生变量，在GWAS流程中最大的全基因组关联研究中调查这些变异与IDD的遗传关联。我们使用两样本MR方法评估这五种MMPs与IDD之间的因果关系。通过逆方差加权（IVW）检验来检验因果效应。并使用IVW的Q检验、MR-Egger、MR-Egger截距和MR-PRESSO进行敏感性分析。
我们发现MMP3血浆水平升高与IDD风险增加之间存在显著相关性（IVW：比值比1.000564，95%置信区间1.0000304 - 1.00110；P = 0.0383）。异质性检验（MR-Egger Q检验：P = 0.346，IVW Q检验：P = 0.460）表明，该工具变量表面上不存在异质性。此外，在MR分析中未观察到方向性水平多效性（MR-Egger，P = 0.708；MR-PRESSO，P = 0.609）。MMP1、MMP7、MMP10和MMP12的血浆水平与IDD风险增加之间无显著相关性。
我们的MR分析发现，在欧洲人群中，MMP3血浆水平升高与IDD风险之间存在潜在因果关系。MMP1、MMP7、MMP10和MMP12的血浆水平与IDD风险增加之间不存在潜在因果关系。
