Exploring Causal Relationships between Circulating Inflammatory Proteins and Thromboangiitis Obliterans: A Mendelian Randomization Study.

Abstract

Background:  Thromboangiitis obliterans (TAO) is a vascular condition characterized by poor prognosis and an unclear etiology. This study employs Mendelian randomization (MR) to investigate the causal impact of circulating inflammatory proteins on TAO.

Methods:  In this MR analysis, summary statistics from a genome-wide association study meta-analysis of 91 inflammation-related proteins were integrated with independently sourced TAO data from the FinnGen consortium's R10 release. Methods such as inverse variance weighting, MR-Egger regression, weighted median approaches, MR-PRESSO, and multivariable MR (MVMR) analysis were utilized.

Results:  The analysis indicated an association between higher levels of C-C motif chemokine 4 and a reduced risk of TAO, with an odds ratio (OR) of 0.44 (95% confidence interval [CI]: 0.29-0.67; p = 1.4 × 10^-4; adjusted p = 0.013). Similarly, glial cell line-derived neurotrophic factor exhibited a suggestively protective effect against TAO (OR: 0.43, 95% CI: 0.22-0.81; p = 0.010; adjusted p = 0.218). Conversely, higher levels of C-C motif chemokine 23 were suggestively linked to an increased risk of TAO (OR: 1.88, 95% CI: 1.21-2.93; p = 0.005; adjusted p = 0.218). The sensitivity analysis and MVMR revealed no evidence of heterogeneity or pleiotropy.

Conclusion:  This study identifies C-C motif chemokine 4 and glial cell line-derived neurotrophic factor as potential protective biomarkers for TAO, whereas C-C motif chemokine 23 emerges as a suggestive risk marker. These findings elucidate potential causal relationships and highlight the significance of these proteins in the pathogenesis and prospective therapeutic strategies for TAO.