Cao Zuoyuan, Zhu Zhujing, Qu Huanru
Department of Rheumatology and Clinical Immunology, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Medicine (Baltimore). 2025 Apr 18;104(16):e42210. doi: 10.1097/MD.0000000000042210.
Previous observational studies have suggested a link between growth factors and Sjögren syndrome, but a definitive causal relationship has yet to be established. We conducted a two-sample Mendelian randomization (MR) study using summary statistics from the FinnGen study on Sjögren syndrome and various growth factors. Analytical techniques included inverse variance weighted, MR-Egger, weighted median, and weighted mode to explore potential causal links. Our analysis indicated that genetically determined growth factors did not have a causal effect on Sjögren syndrome. The inverse variance weighted method showed nonsignificant associations for various exposures, including epidermal growth factor (odds ratios [OR] = 0.94, P = .720), proheparin-binding EGF-like growth factor (OR = 0.95, P = .621), VEGF sR2 (OR = 1.0, P = .988), FGF7 (OR = 1.08, P = .519), PDGF-AA (OR = 0.87, P = .218), VEGF121 (OR = 0.93, P = .466), TGF-β R II (OR = 1.01, P = .934), and NGFI-A-binding protein 2 (OR = 1.13, P = .264). The MR-Egger, weighted median, and weighted mode methods supported these findings. Our study did not find significant causal associations between genetic levels of the studied growth factors and the onset of Sjögren syndrome. Future research should investigate more detailed genetic interactions and modifiable environmental factors to better understand pathways relevant to the prevention and management of Sjögren syndrome.
既往观察性研究提示生长因子与干燥综合征之间存在联系,但尚未确立明确的因果关系。我们利用芬兰基因研究中关于干燥综合征和各种生长因子的汇总统计数据进行了一项两样本孟德尔随机化(MR)研究。分析技术包括逆方差加权法、MR-Egger法、加权中位数法和加权众数法,以探索潜在的因果联系。我们的分析表明,基因决定的生长因子对干燥综合征没有因果效应。逆方差加权法显示,各种暴露因素的关联均无统计学意义,包括表皮生长因子(优势比[OR]=0.94,P=0.720)、前肝素结合表皮生长因子样生长因子(OR=0.95,P=0.621)、血管内皮生长因子sR2(OR=1.0,P=0.988)、成纤维细胞生长因子7(OR=1.08,P=0.519)、血小板衍生生长因子AA(OR=0.87,P=0.218)、血管内皮生长因子121(OR=0.93,P=0.466)、转化生长因子-βR II(OR=1.01,P=0.934)和NGFI-A结合蛋白2(OR=1.13,P=0.264)。MR-Egger法、加权中位数法和加权众数法支持了这些发现。我们的研究未发现所研究生长因子的基因水平与干燥综合征发病之间存在显著的因果关联。未来的研究应调查更详细的基因相互作用和可改变的环境因素,以更好地理解与干燥综合征预防和管理相关的途径。