Department of Gynecology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Beijing University of Chinese Medicine, Beijing, China.
PLoS One. 2024 Sep 12;19(9):e0310292. doi: 10.1371/journal.pone.0310292. eCollection 2024.
Emerging evidence suggests a tentative association between cathepsins and uterine leiomyoma (UL). Previous investigations have predominantly focused on the role of cathepsins in the metastasis and colonization of gynecological malignancies. Still, observational studies may lead to confounding and biases. We employed a bidirectional Mendelian randomization (MR) analysis to elucidate the causative links between various cathepsins and UL. Instrumental variables (IVs) of cathepsins and UL within the European cohort were from extant genome-wide association study datasets. Sensitivity assessments was executed, and the heterogeneity of the findings was meticulously dissected to affirm the solidity of the outcomes. Our findings reveal the association between cathepsin B (CTSB) and an elevated risk of developing UL (all cancers excluded) [Inverse Variance Weighted (IVW) method]: OR = 1.06, 95%CI [1.02, 1.11], P = 0.008895711. Although the association does not persist after multiple testing or Steiger filtering, this finding adds to our understanding of the causal relationship between CTSB of various cathepsins and UL (all cancers excluded) and may herald new therapeutic avenues for individuals affected by this condition.
新出现的证据表明组织蛋白酶与子宫肌瘤(UL)之间存在暂时的关联。之前的研究主要集中在组织蛋白酶在妇科恶性肿瘤的转移和定植中的作用。然而,观察性研究可能会导致混杂和偏倚。我们采用双向孟德尔随机化(MR)分析来阐明各种组织蛋白酶与 UL 之间的因果关系。欧洲队列中组织蛋白酶和 UL 的工具变量(IV)来自现有的全基因组关联研究数据集。我们进行了敏感性评估,并仔细分析了研究结果的异质性,以确认结果的可靠性。我们的研究结果表明组织蛋白酶 B(CTSB)与 UL(排除所有癌症)的发病风险增加之间存在关联[逆方差加权(IVW)法]:OR = 1.06,95%CI [1.02, 1.11],P = 0.008895711。尽管该关联在多次检验或斯泰格过滤后并不存在,但这一发现增加了我们对不同组织蛋白酶的 CTSB 与 UL(排除所有癌症)之间因果关系的理解,并且可能为受这种情况影响的个体开辟新的治疗途径。