Estudo do perfil de genes de reparo do DNA em pacientes com a doença de Parkinson

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disorder among an elderly population, it has no cure and gold therapy for motor symptoms of the disease is levodopa (L-DOPA). In the long term, L-DOPA can lead to adverse symptoms, such as motor fluctuation, dyskinesia and visual hallucinations. And studies show a possible association between oxidative stress (OE) and L-DOPA therapy. The base excision repair (BER) pathway is responsible for controlling the damage caused by OE, the APE1 and XRCC1 proteins being fundamental in this process. Variations in the genes that encode these proteins can affect the efficiency of the repair, making the brain susceptible to damage caused by OE. Thus, the present study aimed to evaluate the relationship between the presence of polymorphisms in the Asp148Glu and Arg399Gln genes of the APE1 and XRCC1 genes, respectively, with the appearance of motor fluctuation, dyskinesia and visual hallucinations with response of the pharmacological response to L-DOPA, in PD patients. 110 patients were obtained from L-DOPA therapy over a period of 5 years. Patients were stratified into two groups according to the daily dosage of L-DOPA, group I taking ≤ 600mg / day and group II taking> 600mg / day. The Asp148Glu and Arg399Gln polymorphisms of the APE1 and XRCC1 genes were performed using the qPCR and PCR-RFLP technique, respectively. The analysis of logistic regression association with longer duration of therapy with L-DOPA (PR 1.1; CI -1.1-1.19; p = 0.001), appearance of motor fluctuation (PR 1.7; CI 1.3-2 , 2; p = 0.001) and the presence of the polymorphic genotype AA of the XRCC1 gene (PR 1.54; CI 1.04-2.27; p = 0.028). In addition to the presence of the GA genotype for the XRCC1 gene providing protection in patients treated with high doses of L-DOPA (PR 0.7; CI 0.5-0.9; p = 0.022). Our data occurred that this variation in the XRCC1 gene can influence the pharmacological response of L-DOPA in patients with PD, whereas the variation in the APE1 gene does not seem to influence the treatment.