慢性单纯性地衣(LSC)由于其难以捉摸的致病机制而在皮肤病学中提出了挑战。虽然观察到循环炎症细胞因子和LSC之间的关联,确定的因果动力学仍有待阐明。我们的研究使用了双样本孟德尔随机化(MR)方法来研究因果关系。我们应用了一套MR方法,包括IVW,加权中位数,MR-Egger,加权模式,简单模式,MR-PRESSO,还有施泰格测试,以确保稳健的因果推理。我们的分析证实了遗传决定的细胞因子水平对LSC风险的因果影响,尤其是MMP-10(OR=0.493,P=0.004)和DNER(OR=0.651,P=0.043)在风险降低方面。我们还发现GDNF水平(OR=1.871,P=0.007)与LSC患病率之间存在正相关。值得注意的是,在DNER和LSC之间观察到双向因果关系。各种MR分析和敏感性分析的一致性证实了水平多效性的缺失,验证因果估计。这项开创性的MR研究揭示了MMP-10,DNER,GDNF和LSC风险。尽管需要进一步验证,我们的发现增强了对LSC中细胞因子介导的理解,并强调了前瞻性研究途径.
Lichen simplex chronicus (LSC) presents a challenge in dermatology due to its elusive pathogenic mechanisms. While associations between circulating inflammatory cytokines and LSC were observed, the definitive causal dynamics remain to be elucidated. Our study used a two-sample Mendelian randomization (MR) approach to investigate causal relationships. We applied a suite of MR methodologies, including IVW, Weighted Median, MR-Egger, Weighted Mode, Simple Mode, MR-PRESSO, and the Steiger test, to ensure robust causal inference. Our analysis confirmed the causal impact of genetically determined cytokine levels on LSC risk, particularly MMP-10 (OR = 0.493, P = 0.004) and DNER (OR = 0.651, P = 0.043) in risk attenuation. We also found a positive causal correlation between GDNF levels (OR = 1.871, P = 0.007) and LSC prevalence. Notably, bidirectional causality was observed between DNER and LSC. Consistency across various MR analyses and sensitivity analyses confirmed the absence of horizontal pleiotropy, validating the causal estimates. This pioneering MR investigation unveils a novel genetically anchored causal relationship between the circulating levels of MMP-10, DNER, and GDNF and LSC risk. Although further validation is requisite, our findings augment the understanding of cytokine mediation in LSC and underscore prospective avenues for research.