■已经报道了组织蛋白酶与前列腺癌(PCa)之间的关系。然而,缺乏对组织蛋白酶和良性前列腺疾病(BPDs)的研究。这项研究通过利用孟德尔随机化(MR)分析来确定是否存在因果关系,调查了组织蛋白酶和BPD之间的潜在遗传联系。
■从FinnGenBiobank获得了有关BPD的公开摘要统计数据。数据包括149,363个人,有30,066例BPH和119,297例对照,和123,057个人,有3,760例和119,297例前列腺炎对照。IEUOpenGWAS提供了10种组织蛋白酶的全基因组关联数据。为了评估BPDs和组织蛋白酶之间的因果关系,采用了五种不同的MR分析,主要方法是逆方差加权(IVW)方法。此外,我们进行了敏感性分析,以检查研究结果的水平多效性和异质性.
■IVWMR检查结果显示,组织蛋白酶O对BPH具有有益作用(IVWOR=0.94,95%CI0.89-0.98,P=0.0055),而组织蛋白酶X对前列腺炎有威胁(IVWOR=1.08,95%CI1.00-1.16,P=0.047)。通过反向MR分析,提示前列腺炎对组织蛋白酶V有不良影响(IVWOR=0.89,95%CI0.80-0.99,P=0.035),而在BPH和组织蛋白酶之间没有观察到有利的关联。从MR-Egger获得的结果,加权中位数,简单模式,和加权模式方法与IVW方法的结果一致。基于敏感性分析,异质性,水平多效性不太可能扭曲结果。
■这项研究提供了组织蛋白酶和BPD之间遗传因果联系的初步证据。我们的发现表明组织蛋白酶O对预防BPH有益,而组织蛋白酶X对前列腺炎有潜在威胁。此外,前列腺炎对组织蛋白酶V水平有负面影响。这三种组织蛋白酶可以作为BPDs诊断和治疗的靶点,这需要进一步的研究。
UNASSIGNED: The relationship between cathepsins and prostate cancer (PCa) has been reported. However, there is a lack of research on cathepsins and benign prostate diseases (BPDs). This study investigated the potential genetic link between cathepsins and BPDs through the utilization of Mendelian randomization (MR) analysis to determine if a causal relationship exists.
UNASSIGNED: Publicly accessible summary statistics on BPDs were obtained from FinnGen Biobank. The data comprised 149,363 individuals, with 30,066 cases and 119,297 controls for BPH, and 123,057 individuals, with 3,760 cases and 119,297 controls for prostatitis. The IEU OpenGWAS provided the Genome-wide association data on ten cathepsins. To evaluate the causal relationship between BPDs and cathepsins, five distinct MR analyses were employed, with the primary method being the inverse variance weighted (IVW) approach. Additionally, sensitivity analyses were conducted to examine the horizontal pleiotropy and heterogeneity of the findings.
UNASSIGNED: The examination of IVW MR findings showed that cathepsin O had a beneficial effect on BPH (IVW OR=0.94, 95% CI 0.89-0.98, P=0.0055), while cathepsin X posed a threat to prostatitis (IVW OR=1.08, 95% CI 1.00-1.16, P=0.047). Through reverse MR analysis, it was revealed that prostatitis had an adverse impact on cathepsin V (IVW OR=0.89, 95% CI 0.80-0.99, P=0.035), while no favorable association was observed between BPH and cathepsins. The results obtained from MR-Egger, weighted median, simple mode, and weighted mode methods were consistent with the findings of the IVW approach. Based on sensitivity analyses, heterogeneity, and horizontal pleiotropy are unlikely to distort the results.
UNASSIGNED: This study offers the initial evidence of a genetic causal link between cathepsins and BPDs. Our findings revealed that cathepsin O was beneficial in preventing BPH, whereas cathepsin X posed a potential threat to prostatitis. Additionally, prostatitis negatively affected cathepsin V level. These three cathepsins could be targets of diagnosis and treatment for BPDs, which need further research.