Clinical-Pharmacogenetic Predictive Models for Time to Occurrence of Levodopa Related Motor Complications in Parkinson ’s Disease

The response to dopaminergic treatments in Parkinson's disease depends on many clinical and genetic factors. The very common motor fluctuations and dyskinesia affect approximately half of patients after five years of treatment with levodopa. We did an evaluation of a combined effect of 16 clinical parameters and 34 single nucleotide polymorphisms to build clinical and clinical-pharmacogenetic models for prediction of time of occurrence of motor complications and to compare their predictive abilities. In total, 220 Parkinson's disease patients were included in the analysis. Their demographic, clinical, and genotype data were obtained. The combined effect of clinical and genetic factors was assessed using The Least Absolute Shrinkage and Selection Operator penalized regression in the Cox proportional hazards model. Clinical and clinical-pharmacogenetic models were constructed. The predictive capacity of the models was evaluated with the cross-validated area under time-dependent receiver operating characteristic curve. Clinical-pharmacogenetic model included age at diagnosis (HR=0.99), time from diagnosis to initiation of levodopa treatment (HR=1.24), COMT rs165815 (HR=0.90), DRD3 rs6280 (HR=1.03), and BIRC5 rs9904341 (HR=0.95) as predictive factors for time to occurrence of motor fluctuations. Furthermore, clinical-pharmacogenetic model for prediction of time to occurrence of dyskinesia included female sex (HR=1.07), age at diagnosis (HR=0.97), tremor-predominant Parkinson’s ...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research