Xie Xiaochao, Song Yanjie, Chen Wenwen, Zhao Hui, Chu Nan, Wang Fang
Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China.
Department of Endocrinology, Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Traditional Chinese Medicine Hospital), Qingdao, People's Republic of China.
Medicine (Baltimore). 2025 May 16;104(20):e42379. doi: 10.1097/MD.0000000000042379.
Clinical studies have consistently demonstrated that inflammation is a critical factor in the pathophysiology and progression of gout. This study aims to explore the causal relationship between CIPs and gout, utilizing MR in conjunction with meta-analyses. We utilized genetic data pertaining to gout from the GWAS which involved 3576 cases and 147,221 control participants. A total of 132 CIPs were extracted from the GWAS data to identify SNPs associated with gout. The primary analytical approach was the IVW method. Sensitivity analyses indicated no pleiotropy or heterogeneity. The IVW results revealed that several CIPs were associated with gout in European populations. The analysis results indicate that FGF-21, MMP-1, G-CSF, and IFN-γ are involved in the pathogenesis of gout, and gout may influence the expression of CXCL1, IL-1Ra, and TNF-α. Consequently, targeted research focusing on specific CIPs could provide a promising strategy for the treatment and prevention of gout, offering potential therapeutic targets for the underlying inflammatory mechanisms of the disease.
临床研究一直表明,炎症是痛风病理生理学和进展中的关键因素。本研究旨在利用孟德尔随机化(MR)结合荟萃分析来探讨因果推断工具变量(CIPs)与痛风之间的因果关系。我们使用了来自全基因组关联研究(GWAS)的痛风相关遗传数据,该研究涉及3576例病例和147221名对照参与者。从GWAS数据中提取了总共132个CIPs,以识别与痛风相关的单核苷酸多态性(SNPs)。主要分析方法是逆方差加权(IVW)法。敏感性分析表明不存在多效性或异质性。IVW结果显示,在欧洲人群中,有几个CIPs与痛风相关。分析结果表明,成纤维细胞生长因子21(FGF-21)、基质金属蛋白酶1(MMP-1)、粒细胞集落刺激因子(G-CSF)和干扰素γ(IFN-γ)参与痛风的发病机制,且痛风可能影响趋化因子配体1(CXCL1)、白细胞介素1受体拮抗剂(IL-1Ra)和肿瘤坏死因子α(TNF-α)的表达。因此,针对特定CIPs的靶向研究可能为痛风的治疗和预防提供一个有前景的策略,为该疾病潜在的炎症机制提供潜在的治疗靶点。