Objective

The contribution of genetic factors to the presence of an overactive bladder is recognized. This study aimed to (1) assemble and synthesize available data from studies assessing differential gene expression in patients with overactive bladder vs controls without overactive bladder and (2) determine possible correlations and functional pathways between genes.

Data Sources

We searched PubMed, Ovid or Medline, and Wiley Cochrane Central Register of Controlled Trials databases between January 1, 2000, and December 15, 2021.

Study Eligibility Criteria

Studies were included if gene expression was detected and quantified using molecular approaches performed on human bladder tissue specimens directly and excluded if the gene expression analysis was carried out from blood and urine specimens alone.

Methods

A systematic review was completed to identify publications that reported differently expressed gene candidates among patients with overactive bladder vs healthy individuals. Gene networking connections and pathway analysis were performed employing Metascape software, where inputs were identified from our systematic review of differentially expressed genes in overactive bladder.

Results

A total of 9 studies were included in the final analysis and 11 genes were identified as being up-regulated (purinergic receptor P2X 2 [P2RX2], smoothelin [SMTN], growth-associated protein 43 [GAP43], transient receptor potential cation channel subfamily M member 8 [TRPM8], cadherin 11 [CDH1], gap junction protein gamma 1 [GJC1], cholinergic receptor muscarinic 2 [CHRM2], cholinergic receptor muscarinic 3 [CHRM3], and transient receptor potential cation channel subfamily V member 4 [TRPV4]) or down-regulated (purinergic receptor P2X 2 [P2RX3] and purinergic receptor P2X 5 [P2RX5]) in patients with overactive bladder. Gene network analysis showed that genes are involved in chemical synaptic transmission, smooth muscle contraction, blood circulation, and response to temperature stimulus. Network analysis demonstrated a significant genetic interaction between TRPV4, TRPM8, P2RX3, and PR2X2 genes.

Conclusion

Outcomes of this systematic review highlighted potential biomarkers for treatment efficacy and have laid the groundwork for developing future gene therapies for overactive bladder in clinical settings.

中文翻译：

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对膀胱过度活动症病例中涉及的潜在遗传标记的系统回顾和计算机研究

 客观的

遗传因素对膀胱过度活动症的影响已得到认可。本研究的目的是（1）收集和合成来自评估膀胱过度活动症患者与无膀胱过度活动症对照的差异基因表达的研究的可用数据，以及（2）确定基因之间可能的相关性和功能途径。

 数据源

我们检索了 2000 年 1 月 1 日至 2021 年 12 月 15 日期间的 PubMed、Ovid 或 Medline 以及 Wiley Cochrane Central Register of Controlled Trials 数据库。

学习资格标准

如果使用直接对人类膀胱组织样本进行的分子方法检测和量化基因表达，则纳入研究；如果仅从血液和尿液样本中进行基因表达分析，则排除研究。

 方法

我们完成了一项系统综述，以确定报告膀胱过度活动症患者与健康个体之间候选基因表达差异的出版物。使用 Metascape 软件进行基因网络连接和通路分析，其中输入是从我们对膀胱过度活动症差异表达基因的系统回顾中确定的。

 结果

最终分析共纳入9项研究，确定11个基因上调（嘌呤能受体P2X 2 [P2RX2]、smoothelin [SMTN]、生长相关蛋白43 [GAP43]、瞬时受体电位阳离子通道亚家族M 成员 8 [TRPM8]、钙粘蛋白 11 [CDH1]、间隙连接蛋白 γ 1 [GJC1]、胆碱能受体毒蕈碱 2 [CHRM2]、胆碱能受体毒蕈碱 3 [CHRM3] 和瞬时受体电位阳离子通道亚家族 V 成员 4 [TRPV4] ]）或在膀胱过度活动症患者中下调（嘌呤能受体 P2X 2 [P2RX3] 和嘌呤能受体 P2X 5 [P2RX5]）。基因网络分析表明，基因参与化学突触传递、平滑肌收缩、血液循环和对温度刺激的反应。网络分析表明 TRPV4、TRPM8、P2RX3 和 PR2X2 基因之间存在显着的遗传相互作用。

 结论

这项系统评价的结果强调了治疗效果的潜在生物标志物，并为未来在临床环境中开发膀胱过度活动症基因疗法奠定了基础。