Downregulation of prenylation machinery genes in peripheral blood of patients with Parkinson’s disease: A pilot study
TL;DR
The findings support dysregulation of the protein prenylation machinery as a potentially informative molecular feature of Parkinson’s disease; however, the contribution of medication exposure and blood-cell composition could not be fully assessed, and independent external validation is required before clinical biomarker utility can be established.
Abstract
Background Parkinson’s disease (PD) is a multifactorial neurodegenerative disorder, and peripheral blood-based biomarkers may help capture disease-related molecular changes. Because protein prenylation is essential for Rab-mediated intracellular trafficking, we investigated whether genes encoding key prenylation enzymes are dysregulated in PD. Methods Peripheral blood samples were collected from patients with PD and healthy controls. Quantitative real-time PCR was performed for FNTA, FNTB, RABGGTA, RABGGTB, and PGGT1B, using B2M as the endogenous reference gene. Expression was analyzed with efficiency-adjusted ΔCt calculations, and group comparisons, regression analyses, correlation testing, and ROC analyses were performed using standard nonparametric and multivariable approaches. Results Four genes, FNTA, FNTB, RABGGTB, and PGGT1B, were significantly downregulated in PD, whereas RABGGTA showed only a weak, non-significant decrease. Individual ROC analyses showed good-to-excellent diagnostic performance for FNTA, FNTB, RABGGTB, and PGGT1B, while RABGGTA performed poorly. A multigene logistic regression model combining FNTA, FNTB, RABGGTB, and PGGT1B yielded excellent discrimination between PD and controls (AUC = 0.9787), with 90.0% overall classification accuracy and satisfactory model calibration. Correlation analyses further suggested coordinated expression patterns among the studied genes, supporting a pathway-level disturbance. Conclusion This pilot study identifies coordinated alterations in peripheral expression of prenylation-related genes in Parkinson’s disease. The findings support dysregulation of the protein prenylation machinery as a potentially informative molecular feature of Parkinson’s disease; however, the contribution of medication exposure and blood-cell composition could not be fully assessed, and independent external validation is required before clinical biomarker utility can be established.