Investigating the causal relationship between CD39 + secreting Treg cells and intervertebral disc degeneration (IVDD) and identifying and quantifying the role of pimelylcarnitine (C7-DC) as a potential mediator. Using summary-level data from a genome-wide association study, a two-sample Mendelian randomization (MR) analysis of genetically predicted CD39 + secreting Treg (N = 3045) and IVDD (41,669 cases, 294,770 controls) was performed. Furthermore, two-step MR was used to quantitate the proportion of the effect of C7-DC protein-mediated RA on IVDD. MR analysis identified higher genetically predicted CD39 + secreting Treg on immune cells (primary MR analysis odds ratio (OR) 1.02/SD increase, 95% confidence interval CI: 1.01–1.03) increased risk of IVDD. There was no strong evidence that genetically predicted IVDD had an effect on CD39 + secreting Treg (OR: 0.58, 95% CI: 0.23–1.49). The proportion of genetically predicted IVDD mediated by C7-DC was 9.1%. In conclusion, the present study identifies a causal relationship between CD39 + secreting Tregs in immune cells and IVDD. A small proportion of the effect is mediated by C7-DC, whereas the majority of the mechanism underlying the effect of CD39 + secreting Tregs on IVDD remains unclear. These findings may provide novel therapeutic targets and offer valuable insights for further investigations into the underlying mechanisms.
Li et al. (Fri,) studied this question.