Polymorphisms of Dopamine Receptor Genes and Risk of L-Dopa–Induced Dyskinesia in Parkinson’s Disease

Sampaio

Journal of Pharmacy and Pharmacology

et al. 2018

Objectives The aim of this study was to evaluate a possible relationship between DRD2/ANKK1 (rs1800497) and SLC6A3/DAT1 (rs28363170) gene polymorphisms with the response to levodopa (L‐DOPA)‐therapy in patients with Parkinson's disease (PD). Methods One hundred and ninety‐five patients with idiopathic PD were investigated. Patients were genotyped for rs1800497 and rs28363170 polymorphisms using PCR‐RFLP. Logistic regression was performed to assess the association of polymorphisms with the occurrence of the chronic complications of L‐DOPA therapy. Key findings Our results showed association between the occurrence of dyskinesia with an increased greater disease severity (P = 0.007), higher L‐DOPA dose (P = 0.007) and use of dopamine agonist (P = 0.020). Moreover, there were significant protective effects for age (P = 0.004) and male subjects (P = 0.006). Conclusions Clinical and demographic characteristics of Brazilian PD patients and differences in DRD2 and DAT1 genes may to determine individual variations in the therapeutic response to L‐DOPA in the Brazilian PD patients.

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The influence of SLC6A3 and DRD2 polymorphisms on levodopa-therapy in patients with sporadic Parkinson's disease

Sampaio

Journal of Pharmacy and Pharmacology

et al. 2018

“…To date, strong evidence supports a genetic component in PD susceptibility, whereas studies showing a relevant role for disease modifying genes are less represented [21,22,23]. This might be due, at least in part, to the difficulty in collecting data on disease evolution compared to recording disease development.…”

Section: Resultsmentioning

confidence: 85%

The Role of SNCA Rep1 Microsatellite in Parkinson’s Disease Progression

Corrado¹,

Marchi²,

Tùnesi³

et al. 2017

Preprint

Self Cite

Abstractα-synuclein is a constituent of Lewy bodies and mutations of its gene cause familial PD. A previous study showed that a variant of α-synuclein gene (SNCA), namely the 263bp allele of Rep1 was associated to faster motor progression in PD. On the contrary, a recent report failed to detect a detrimental effect of Rep1 263 on both motor and cognitive outcomes in PD. Aim of this study was to evaluate the influence of the Rep1 variants on disease progression in Parkinson's Disease (PD) patients. We recruited and genotyped for SNCA-Rep1 426 PD patients with age at onset ≥40 years and disease duration ≥4 years. We then analyzed frequency and time of occurrence of wearing-off, dyskinesia, freezing of gait, visual hallucinations and dementia. SNCA Rep1 263 carriers showed increased risk of both dementia (HR=3.03) and visual hallucinations (HR=2.69) compared to 263 non-carriers. In conclusion, SNCA Rep 1 263 allele is associated to a worst cognitive outcome in PD.

“…Therefore, we suspect that individuals with BR have their own specificity, as described previously, 14 and it may involve a certain susceptibility. However, the specific mechanism may be related to the polymorphism of the dopamine receptor gene, which increases the risk of LID 15,16 …”

Section: Discussionmentioning

confidence: 99%

Analysis of factors associated with brittle response in patients with Parkinson’s disease

Yan

Liu

et al. 2020

Ann Clin Transl Neurol

Introduction: The brittle response (BR) in patients with Parkinson's disease (PD) refers to a special type of levodopa-induced dyskinesia (LID). This study aimed to describe the clinical characteristics of BR patients and to analyze the associated risk factors. Methods: A retrospective study was conducted to analyze the data of 97 patients with PD. Patients were divided into a BR group and a non-brittle response (NBR) group. Demographic and clinical data, motor symptoms, and non-motor symptoms of the two groups were assessed. Results: Among 97 PD patients, 11 were in the BR group and 86 were in the NBR group. The proportion of female patients was 72.7% and 38.3%, respectively, in the BR and NBR groups (P < 0.05). Compared to NBR patients, BR patients had relatively low body weight, low BMI, long disease duration, high levodopa equivalent daily dosage (LEDD), and high levodopa dose per weight (P < 0.05). The BR group had significantly higher scores of UPDRS (II, III, and IV) (P < 0.05). But no difference was found in the UPDRS I, emotional state, cognitive status, and accompanied by REM sleep behavior disorder (RBD) (P> 0.05). Multivariate logistic regression analysis showed that BR patients had lower body weight and higher levodopa dose per weight. Conclusion: BR is associated with being female, low body weight, low BMI, long disease duration, high LEDD, and high levodopa dose per weight. Body weight and levodopa dose per body weight are independent risk factors for BR.