Changde Hospital, Xiangya School of Medicine, Central South University (The First People's Hospital of Changde City), Changde, China.
Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
Front Immunol. 2024 Oct 18;15:1452801. doi: 10.3389/fimmu.2024.1452801. eCollection 2024.
The current landscape of acne therapeutics is notably lacking in targeted treatments, highlighting a critical need for the discovery of new drug targets to improve treatment outcomes.
This study aims to investigate the connections between proteomics and genetics in relation to acne across extensive population cohorts, aspiring to identify innovative preventive and therapeutic approaches.
Employing a longitudinal cohort of 54,306 participants from the UK Biobank Pharmacological Proteomics Project (UKB-PPP), we performed an exhaustive evaluation of the associations between 2,923 serum proteins and acne risk. Initial multivariate Cox regression analyses assessed the relationship between protein expression levels and acne onset, followed by two-sample Mendelian Randomization (TSMR), Summary-data-based Mendelian Randomization (SMR), and colocalization to identify genetic correlations with potential protein targets.
Within the UKB cohort, we identified 19 proteins significantly associated with the risk of acne. Subsequent analysis using Two-Sample Mendelian Randomization (TSMR) refined this to two specific proteins: FSTL1 and ANXA5. Each one-standard deviation increase in the expression levels of FSTL1 and ANXA5 was associated with a 24% and 32% increase in acne incidence, respectively. These results were further validated by additional Summary-data-based Mendelian Randomization (SMR) and differential expression analyses.
Our comprehensive analysis of proteomic and genetic data from a European adult cohort provides compelling causal evidence that several proteins are promising targets for novel acne treatments.
目前的痤疮治疗领域明显缺乏靶向治疗方法，这突显了发现新的药物靶点以改善治疗效果的迫切需求。
本研究旨在通过广泛的人群队列，研究蛋白质组学和遗传学与痤疮之间的关联，以期发现创新的预防和治疗方法。
我们利用来自英国生物库药物蛋白质组学项目（UKB-PPP）的 54306 名参与者的纵向队列，对 2923 种血清蛋白与痤疮风险之间的关联进行了全面评估。最初的多变量 Cox 回归分析评估了蛋白质表达水平与痤疮发病之间的关系，然后进行两样本 Mendelian Randomization（TSMR）、基于汇总数据的 Mendelian Randomization（SMR）和共定位分析，以确定与潜在蛋白质靶标具有遗传相关性的基因。
在 UKB 队列中，我们确定了 19 种与痤疮风险显著相关的蛋白质。使用两样本 Mendelian Randomization（TSMR）的进一步分析将其缩小到两种特定的蛋白质：FSTL1 和 ANXA5。FSTL1 和 ANXA5 的表达水平每增加一个标准差，痤疮发病率分别增加 24%和 32%。这些结果通过额外的基于汇总数据的 Mendelian Randomization（SMR）和差异表达分析得到了进一步验证。
我们对来自欧洲成年人群队列的蛋白质组学和遗传数据的综合分析提供了令人信服的因果证据，表明几种蛋白质是新型痤疮治疗的有前途的靶标。
