Yan Kun, Tao Yifang, Chen Bohong, Zhang Dong, Li Zihao, Li Caogang, Zhang Peng
Department of Urology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157, Xiwu Rd., Xi'an, 710004, Shaanxi Province, China.
Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaan'xi Province, China.
Sci Rep. 2025 May 30;15(1):19069. doi: 10.1038/s41598-025-03510-w.
Prostatitis is a common condition in andrology and urology that significantly impacts the quality of life of affected individuals. Current treatments often fail to provide lasting benefits. To identify novel therapeutic targets, we conducted a drug-targeted Mendelian randomization (MR) study. Using cis-expression quantitative trait loci (cis-eQTL) data from the eQTLGen Consortium combined with Genome-Wide Association Studies (GWAS) data on prostatitis from FinnGen, we performed a two-sample MR analysis. This analysis identified nine potential causal genes: ANXA1, CRY2, DSTYK, FKBP1A, LAMA5, NENF, PTGIR, STK39, and TGFA. Following heterogeneity testing, horizontal pleiotropy assessment, and bidirectional MR, CRY2 and PTGIR were validated in the Genotype-Tissue Expression (GTEx) portal replication phase. Bayesian colocalization analysis and genetic correlation analysis investigations provided strong evidence of shared causal variants with prostatitis and negative genetic correlations for these genes. PheWAS indicated negligible horizontal pleiotropy, and drug prediction analysis identified potential targeting agents for CRY2 and PTGIR. This study highlights CRY2 and PTGIR as promising therapeutic targets for prostatitis, providing new insights into its genetic underpinnings and offering potential pathways for developing effective treatments.
前列腺炎是男科和泌尿外科的常见病症，严重影响患者的生活质量。目前的治疗方法往往无法提供持久的疗效。为了确定新的治疗靶点，我们进行了一项药物靶向孟德尔随机化（MR）研究。利用来自eQTLGen联盟的顺式表达定量性状位点（cis-eQTL）数据，并结合芬兰基因库中关于前列腺炎的全基因组关联研究（GWAS）数据，我们进行了两样本MR分析。该分析确定了九个潜在的因果基因：膜联蛋白A1（ANXA1）、隐花色素2（CRY2）、双特异性酪氨酸磷酸化调节激酶（DSTYK）、FK506结合蛋白1A（FKBP1A）、层粘连蛋白α5（LAMA5）、神经内分泌因子（NENF）、前列腺素I2受体（PTGIR）、丝氨酸/苏氨酸蛋白激酶39（STK39）和转化生长因子α（TGFA）。经过异质性检验、水平多效性评估和双向MR分析，CRY2和PTGIR在基因型-组织表达（GTEx）数据库的复制阶段得到了验证。贝叶斯共定位分析和遗传相关性分析调查提供了与前列腺炎共享因果变异以及这些基因负遗传相关性的有力证据。表型全基因组关联研究（PheWAS）表明水平多效性可忽略不计，药物预测分析确定了CRY2和PTGIR的潜在靶向药物。这项研究突出了CRY2和PTGIR作为前列腺炎有前景的治疗靶点，为其遗传基础提供了新的见解，并为开发有效治疗方法提供了潜在途径。
