Luo Hui, Chen Yang, Li Jianrong, Yang Yanmei, Wang Xiujun, Yang Ping, Guo Chuang, Liu Fei
Department of Traditional Chinese Medicine, People's Hospital of Xiangyun County, Dali, China.
J Dermatol. 2025 Mar;52(3):481-492. doi: 10.1111/1346-8138.17590. Epub 2024 Dec 20.
Previous research has highlighted a significant association between inflammatory proteins and the development and progression of hidradenitis suppurativa (HS). Nevertheless, the potential causative link between these factors remains to be definitively established. To investigate the genetic correlation between inflammatory proteins and HS, linkage disequilibrium score regression (LDSC) was employed. Mendelian randomization (MR) analysis, incorporating inverse variance weighted, MR-Egger, and weighted median methodologies, was utilized to evaluate the possible causal relationship between circulating inflammatory proteins (CIPs) and HS. Additionally, reverse MR analysis was carried out to explore reverse causality. The data set for 91 CIPs was derived from a genome-wide protein quantitative trait loci study, while HS-related data were acquired from the FinnGen study. Moreover, the stability of the causal relationships was assessed via sensitivity analyses, encompassing tests for pleiotropy, heterogeneity, and leave-one-out analysis. The LDSC analysis suggested the existence of genetic correlations between the levels of Fibroblast growth factor 21 (FGF-21), stem cell factor, and HS. The MR analysis identified a suggestive association of T-cell surface glycoprotein CD5 and C-X-C motif chemokine 11 with an elevated risk of HS. Conversely, C-C motif chemokine 4, Protein S100-A12, Interleukin-10 receptor subunit beta, and Programmed cell death 1 ligand 1 were associated with a diminished risk of HS. Moreover, HS was demonstrated to increase the levels of four CIPs: Interleukin-20, Leukemia inhibitory factor (LIF), LIF receptor, and Thymic stromal lymphopoietin. The findings of this investigation offer suggestive evidence for possible genetic correlations and causal links between various genetically predicted inflammatory proteins and HS. There exists a pressing requirement for additional studies to elucidate the fundamental processes driving these associations.
先前的研究强调了炎症蛋白与化脓性汗腺炎（HS）的发生和发展之间存在显著关联。然而，这些因素之间潜在的因果联系仍有待明确确立。为了研究炎症蛋白与HS之间的遗传相关性，采用了连锁不平衡评分回归（LDSC）方法。利用孟德尔随机化（MR）分析，结合逆方差加权、MR-Egger和加权中位数方法，评估循环炎症蛋白（CIPs）与HS之间可能的因果关系。此外，还进行了反向MR分析以探索反向因果关系。91种CIPs的数据集来自全基因组蛋白质定量性状位点研究，而HS相关数据则从芬兰基因研究中获取。此外，通过敏感性分析评估因果关系的稳定性，包括多效性检验、异质性检验和留一法分析。LDSC分析表明成纤维细胞生长因子21（FGF-21）、干细胞因子水平与HS之间存在遗传相关性。MR分析确定T细胞表面糖蛋白CD5和C-X-C基序趋化因子11与HS风险升高存在提示性关联。相反，C-C基序趋化因子4、蛋白S100-A12、白细胞介素-10受体亚基β和程序性细胞死亡1配体1与HS风险降低相关。此外，研究表明HS会增加四种CIPs的水平：白细胞介素-20、白血病抑制因子（LIF）、LIF受体和胸腺基质淋巴细胞生成素。本研究结果为各种遗传预测的炎症蛋白与HS之间可能的遗传相关性和因果联系提供了提示性证据。迫切需要更多研究来阐明驱动这些关联的基本过程。
