Department of Joint Surgery, HongHui Hospital, Xi'an Jiaotong University, Xi'an, Shanxi 710054, China.
Department of Endocrinology, Xi'an Central Hospital, Xi'an, Shaanxi 710003, China.
Cytokine. 2024 Jul;179:156625. doi: 10.1016/j.cyto.2024.156625. Epub 2024 Apr 26.
Previous traditional observational studies have suggested the contribution of several cytokines and growth factors to the development of osteoarthritis (OA). This study aimed to determine the association of circulating cytokine and growth factor levels with OA.
We used two-sample Mendelian randomization (MR) to explore the causality between circulating cytokine and growth factor levels and OA [including knee or hip OA (K/HOA), knee OA (KOA), and hip OA (HOA)]. Summary level data for circulating cytokine and growth factor levels were sourced from a genome-wide association study (GWAS) involving 8,293 participants of Finnish ancestry. Single-nucleotide polymorphisms related to K/HOA (39,427 cases and 378,169 controls), KOA (24,955 cases and 378,169 controls), and HOA (15,704 cases and 378,169 controls) were obtained from a previous GWAS. The inverse variance weighted (IVW) method was primarily used for our MR analysis. For exposures to only one relevant SNP as IV, we used the Wald ratio as the major method to assess causal effects. We also conducted a series of sensitivity analyses to improve the robustness of the results.
Circulating vascular endothelial growth factor levels were suggestively associated with an increased risk of K/HOA (odds ratio (OR) = 1.034; 95 % confidence interval (CI) = 1.013-1.055; P = 0.001), KOA (OR = 1.034; 95 % CI = 1.014-1.065; P = 0.002), and HOA (OR = 1.039; 95 % CI = 1.003-1.067; P = 0.034). Circulating interleukin (IL)-12p70 levels was suggestively associated with K/HOA (OR = 1.047; 95 % CI = 1.018-1.077; P = 0.001), KOA (OR = 1.058; 95 % CI = 1.022-1.095; P = 0.001), and HOA (OR = 1.044; 95 % CI = 1.000-1.091; P = 0.048). Circulating IL-18 levels were suggestively associated with HOA (OR = 1.068; 95 % CI = 1.014-1.125; P = 0.012). However, limited evidence exists to support causal genetic relationships between other circulating cytokines, growth factor levels and K/HOA, KOA, and HOA.
Our MR analysis provides suggestive evidence of causal relationships between circulating cytokines and growth factors levels and OA, providing new insights into the etiology of OA.
先前的传统观察性研究表明，几种细胞因子和生长因子对骨关节炎（OA）的发展有一定影响。本研究旨在确定循环细胞因子和生长因子水平与 OA 之间的关联。
我们使用两样本 Mendelian 随机化（MR）来探讨循环细胞因子和生长因子水平与 OA[包括膝或髋关节 OA（K/HOA）、膝 OA（KOA）和髋关节 OA（HOA）]之间的因果关系。循环细胞因子和生长因子水平的汇总水平数据来自一项涉及 8293 名芬兰血统参与者的全基因组关联研究（GWAS）。与 K/HOA（39427 例病例和 378169 例对照）、KOA（24955 例病例和 378169 例对照）和 HOA（15704 例病例和 378169 例对照）相关的单核苷酸多态性（SNP）来自之前的 GWAS。我们主要使用逆方差加权（IVW）方法进行 MR 分析。对于仅有一种相关 SNP 作为暴露的情况，我们使用 Wald 比作为主要方法来评估因果效应。我们还进行了一系列敏感性分析，以提高结果的稳健性。
循环血管内皮生长因子水平与 K/HOA（比值比（OR）=1.034；95%置信区间（CI）=1.013-1.055；P=0.001）、KOA（OR=1.034；95%CI=1.014-1.065；P=0.002）和 HOA（OR=1.039；95%CI=1.003-1.067；P=0.034）的发病风险呈显著正相关。循环白细胞介素（IL）-12p70 水平与 K/HOA（OR=1.047；95%CI=1.018-1.077；P=0.001）、KOA（OR=1.058；95%CI=1.022-1.095；P=0.001）和 HOA（OR=1.044；95%CI=1.000-1.091；P=0.048）呈显著正相关。循环白细胞介素-18 水平与 HOA 呈显著正相关（OR=1.068；95%CI=1.014-1.125；P=0.012）。然而，目前仅有有限的证据支持其他循环细胞因子、生长因子水平与 K/HOA、KOA 和 HOA 之间存在因果遗传关系。
我们的 MR 分析提供了循环细胞因子和生长因子水平与 OA 之间存在因果关系的提示性证据，为 OA 的病因学提供了新的见解。
