Genetically predicted serum Pimelylcarnitine mediates the association between CD39+ secreting Treg cells and...

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.