Hou Ruolin, Liu Xin, Zhang Changzhen, Cai Shuiqi, Liu Chengyi, Huang Qun
The Third People's Hospital Health Care Group of Cixi, Ningbo, China.
Ningbo No. 2 Hospital, Ningbo, China.
Medicine (Baltimore). 2024 Dec 13;103(50):e40988. doi: 10.1097/MD.0000000000040988.
Rheumatoid arthritis (RA) is a chronic autoimmune disease that significantly impacts the quality of life of affected individuals. Observational data have consistently pointed towards an associative relationship between cathepsins and the development of RA. Nonetheless, the establishment of a definitive causal nexus between members of the cathepsin family and the pathogenesis of RA remains elusive. In this study, we harnessed the principles of Mendelian randomization (MR) to interrogate the putative causal association between cathepsins and RA, and a series of sensitivity analyses were used to test the reliability of the MR results. Forward MR analyses substantiated a significant genetic correlation between the genetically predicted levels of Cathepsin B and the predisposition to RA, elevated levels of Cathepsin B exhibit a significant association with an increased risk of RA (OR = 1.0727, 95% CI: 1.0171-1.1314, P = .0098). In the reverse MR and multivariable MR analyses, no significant causal relationship was identified between cathepsins and RA. The findings suggest that Cathepsin B may serve as a biomarker for RA, thereby offering significant implications for the advancement of diagnostic and therapeutic strategies in the management of RA.
类风湿性关节炎(RA)是一种慢性自身免疫性疾病,会严重影响患者的生活质量。观察性数据一直表明组织蛋白酶与RA的发展之间存在关联关系。然而,组织蛋白酶家族成员与RA发病机制之间明确的因果联系仍不明确。在本研究中,我们利用孟德尔随机化(MR)原理来探究组织蛋白酶与RA之间的假定因果关联,并使用一系列敏感性分析来检验MR结果的可靠性。正向MR分析证实,组织蛋白酶B的基因预测水平与RA易感性之间存在显著的遗传相关性,组织蛋白酶B水平升高与RA风险增加显著相关(OR = 1.0727,95% CI:1.0171 - 1.1314,P = 0.0098)。在反向MR和多变量MR分析中,未发现组织蛋白酶与RA之间存在显著的因果关系。研究结果表明,组织蛋白酶B可能作为RA的生物标志物,从而为RA管理中诊断和治疗策略的进展提供重要启示。