Circulating cytokines levels and osteoarthritis: A Mendelian randomization study

Jiale Xie; Xianjie Wan; Mingyi Yang; Hui Yu; Jinrong Hao; Ke Xu; Jiachen Wang; Peng Xu

doi:10.1016/j.cyto.2024.156625

Circulating cytokines levels and osteoarthritis: A Mendelian randomization study

Cytokine. 2024 Apr 26:179:156625. doi: 10.1016/j.cyto.2024.156625. Online ahead of print.

Authors

Jiale Xie¹, Xianjie Wan¹, Mingyi Yang¹, Hui Yu¹, Jinrong Hao², Ke Xu¹, Jiachen Wang¹, Peng Xu³

Affiliations

¹ Department of Joint Surgery, HongHui Hospital, Xi'an Jiaotong University, Xi'an, Shanxi 710054, China.
² Department of Endocrinology, Xi'an Central Hospital, Xi'an, Shaanxi 710003, China.
³ Department of Joint Surgery, HongHui Hospital, Xi'an Jiaotong University, Xi'an, Shanxi 710054, China. Electronic address: xupeng369@mail.xjtu.edu.cn.

PMID: 38677184
DOI: 10.1016/j.cyto.2024.156625

Abstract

Background: 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.

Methods: 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.

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.

Conclusions: 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.

Keywords: Circulating cytokines levels; Circulating growth factors levels; Mendelian randomization; Osteoarthritis; Single-nucleotide polymorphisms.