基于蛋白质组学数据的银屑病蛋白-年龄交互作用研究

doi:10.3969/j.issn.1003-9198.2026.10.006

摘要/Abstract

摘要： 目的基于蛋白质组学数据,探索银屑病风险相关的蛋白质-年龄交互作用。方法纳入英国生物标本库(UK Biobank)2006年4月至2010年10月完成基线调查且具有蛋白质组学数据的成年参与者共51 283名,根据是否患有银屑病将其分为病例组(n=1 112)和对照组(n=50 171)。应用基于正则化回归的基因-环境交互作用方法(GESSO)筛选蛋白质-年龄交互作用,并通过logistic逐步回归进行检验,保留P<0.05的交互作用。基于人群特征及交互作用信号构建风险模型,并绘制ROC曲线,采用AUC评估交互作用的风险分层能力。结果共鉴定出2个蛋白与年龄存在交互作用,均与银屑病存在显著关联(FCGR3B:OR_交互作用=0.978, 95%CI: 0.965～0.991;PAPPA:OR_交互作用=1.022, 95%CI: 1.008～1.036)。按年龄分层(<65岁和≥65岁)分析显示,两个蛋白与银屑病的关联仅在老年人群中具有统计学意义,在非老年人群中无显著关联。FCGR3B蛋白与银屑病呈显著负向关联(OR=0.773, 95%CI: 0.618～0.971, P=0.026);而PAPPA蛋白则与银屑病呈显著正向关联(OR=1.460, 95%CI: 1.148～1.866, P=0.002)。蛋白质-年龄交互作用使得模型AUC提升了4.17%(P=0.042)。结论蛋白质FCGR3B、PAPPA与年龄存在交互,并通过复杂机制与银屑病存在关联,为蛋白质靶向干预提供人群层面证据。

关键词: 银屑病, 蛋白质, 年龄, 交互作用

Abstract: Objective To explore protein-age interactions associated with psoriasis based on proteomic data. Methods A total of 51 283 adult participants from the UK Biobank who completed the baseline assessment from April, 2006 to October, 2010 and had available proteomic data were included in this study. Participants were classified into psoriasis case group(n=1 112) and control group(n=50 171) according to psoriasis status. Regularized regression-based gene-environment interaction approach(Gene-by-Environment Lasso, GESSO) was applied to screen potential protein-age interactions. The interactions were further validated using stepwise logistic regression model, and those with P < 0.05 were retained. A risk model was developed based on participants’ characteristics and protein-age interactions. Model performance was evaluated using receiver operating characteristic(ROC) curves and the area under the ROC curve(AUC). Results Two proteins were identified to interact with age and were significantly associated with psoriasis (FCGR3B: OR_interaction=0.978, 95%CI: 0.965-0.991; PAPPA: OR_interaction=1.022, 95%CI: 1.008-1.036). Age-stratified analysis(<65 years and ≥65 years) showed that both proteins were statistically significant associated with psoriais only among elderly participants, whereas no significant associations were observed in non-elderly participants. FCGR3B was significantly inversely associated with psoriasis (OR=0.773, 95%CI: 0.618-0.971), whereas PAPPA was significantly positively associated with psoriasis (OR=1.460, 95%CI: 1.148-1.866). Protein-age interaction significantly improved model performance, with an increase of 4.17% in AUC(P=0.042). Conclusions FCGR3B and PAPPA exhibit significant interactions with age, and were associated with psoriasis risk through complex association patterns. These findings provide population-level evidence for potential protein-targeted interventions.

Key words: psoriasis, protein, age, interaction

中图分类号:

R181

陈丹丹, 周嘉澄, 张汝阳. 基于蛋白质组学数据的银屑病蛋白-年龄交互作用研究[J]. 实用老年医学, 2026, 40(10): 1006-1011.

CHEN Dandan, ZHOU Jiacheng, ZHANG Ruyang. A protein-age interaction study of psoriasis based on proteomic data[J]. Practical Geriatrics, 2026, 40(10): 1006-1011.

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