Downregulation of prenylation machinery genes in peripheral blood of patients with Parkinson's disease: A pilot study.
Downregulation of prenylation machinery genes in peripheral blood of patients with Parkinson's disease: A pilot study.
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Original 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.