Mao Rui, Wang Fan, Zhang Tongtong, Li Ji
Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
Hunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, China.
Exp Dermatol. 2025 Sep;34(9):e70161. doi: 10.1111/exd.70161.
The current therapeutic landscape for rosacea is notably deficient in targeted medications, underscoring an urgent need for the identification of novel biomarkers. Utilising a longitudinal cohort of 54 306 individuals from the UK Biobank (UKB), we conducted a comprehensive assessment of the associations between 2923 serum proteins and the risk for rosacea. Our cohort analysis identified 18 proteins significantly associated with rosacea risk. Next, we complemented the two-sample Mendelian randomisation (TSMR) and Mendelian randomisation (SMR) analysis based on pooled data to identify genetic links between protein targets and rosacea. TSMR analysis refined this list to nine proteins demonstrating significant causal relationships with at least one form of rosacea. Further refinement through SMR and differential expression analysis reduced this to five key proteins, including four (ABHD14B, CHMP6, DBNL and MCFD2) that inhibit rosacea onset and one (MSR1) that promotes it. The differential expression of these five biomarkers was validated by multiple omics datasets as well as in vitro experiments. We calculated the protein score based on the expression levels of these proteins, noting that participants with higher scores demonstrated an increased incidence of rosacea. The integrative examination of proteomic and genetic data from a European adult cohort provides robust causal evidence for several proteins as promising new biomarkers for the development of rosacea treatments.
目前酒渣鼻的治疗领域明显缺乏靶向药物，这凸显了识别新型生物标志物的迫切需求。我们利用来自英国生物银行（UKB）的54306名个体的纵向队列，对2923种血清蛋白与酒渣鼻风险之间的关联进行了全面评估。我们的队列分析确定了18种与酒渣鼻风险显著相关的蛋白。接下来，我们基于汇总数据补充了两样本孟德尔随机化（TSMR）和孟德尔随机化（SMR）分析，以确定蛋白靶点与酒渣鼻之间的遗传联系。TSMR分析将该列表细化为9种蛋白，这些蛋白与至少一种形式的酒渣鼻存在显著因果关系。通过SMR和差异表达分析进一步细化后，减少到5种关键蛋白，其中4种（ABHD14B、CHMP6、DBNL和MCFD2）抑制酒渣鼻发作，1种（MSR1）促进酒渣鼻发作。这5种生物标志物的差异表达在多个组学数据集以及体外实验中得到了验证。我们根据这些蛋白的表达水平计算了蛋白评分，注意到评分较高的参与者酒渣鼻发病率增加。对欧洲成年队列的蛋白质组学和遗传数据进行综合检查，为几种蛋白提供了有力的因果证据，这些蛋白有望成为开发酒渣鼻治疗方法的新生物标志物。
