Pharmacogenetic profile and the development of the dyskinesia induced by levodopa-therapy in Parkinson’s disease patients: a population-based cohort study

Santos, Erinaldo Ubirajara Damasceno dos; Silva, Isaura Isabelle Fonseca Gomes da; Asano, Amdore Guescel; Asano, Nadja Maria Jorge; Maia, Maria de Mascena Diniz; Souza, Paulo Roberto Eleutério de

doi:10.1007/s11033-020-05956-9

Cited by 8 publications

(6 citation statements)

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“…Sampaio et al, 23 also found that the COMT L/L genotype of rs4680 was associated with risk of dyskinesia development after adjusting for age and sex. The study by dos Santos et al 24 has shown an increased risk of dyskinesia in the rs4680 LL genotype. Other than these 3 studies included in the meta-analysis showing association of AA genotype with LID in PD, a study by De Lau et al 25 has also reported that the AA genotype was associated with a significantly increased risk of developing dyskinesia during follow up, results were not attenuated after additional adjustment for duration and dose of L-Dopa and dopamine agonists.…”

Section: Discussionmentioning

confidence: 94%

“…This meta-analysis includes 9 studies for the investigation of the association between COMT rs4680 SNP (G>A, Val158Met) and risk for development of LID. 3 studies have reported the association for AA genotype with dyskinesia in PD patients (Watanabe et al 2003, Sampaio et al 2018, dos Santos et al 2020) 22-24 while 6 studies did not find any significant association (Cheshire et al 2013; Contin et al 2005; Kakinuma et al 2020; Sampaio et al 2018; Torkaman-Boutorabi et al 2012; Xiao Q et al 2017).…”

Section: Discussionmentioning

confidence: 99%

“…7,8 Several studies have investigated the association between COMT rs4680 (Val158Met) polymorphism and LID risk but have provided inconsistent results. Some studies reported that COMT rs4680 is associated with LID (de Lau et al 2012;Sampaio et al 2018;dos Santos et al 2020;Watanabe et al 2003), while others found no association with LID susceptibility. [9][10][11][12] Conflicting results of these studies might be due to the small sample size, different ethnicity of subjects, different recruiting criteria, and various clinical factors.…”

Section: Introductionmentioning

confidence: 99%

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Association of Catechol-O-Methyltransferase Gene rs4680 Polymorphism and Levodopa Induced Dyskinesia in Parkinson’s Disease: A Meta-Analysis and Systematic Review

Dwivedi

Kumar

et al. 2022

J Geriatr Psychiatry Neurol

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Introduction Long-term levodopa therapy for Parkinson’s disease (PD) can cause levodopa induced dyskinesia (LID). Genetic predisposition has a significant role to play in inter-individual heterogeneity in the clinical manifestation of LID. Despite accumulating evidence for the role of COMT gene polymorphism (rs4680) as a genetic basis for LID, to date results have been inconsistent. Early assessment of the Catechol-O-Methyltransferase (COMT) genotype might be helpful to stratify PD patients concerning their individual risk for LID. Method In this meta-analysis, we have used 9 studies, which were selected through online databases. Statistical analysis was performed using R (v-3.6) software. 5 genetic models have been used in the present study: Allele model (A vs. G), Dominant model (AA+AG vs. GG), Homozygote model (AA vs. GG), Co-dominant/heterozygote model (AG vs. GG), and Recessive model (AA vs. AG + GG). Results The results indicated a significant association between COMT rs4680 (Val158Met) polymorphism and LID risk. The genotype AA of COMT rs4680 is a risk factor for LID in PD patients under the recessive model (AA vs GG+AG) in the random-effect model. Analysis based on ethnicity showed that COMT rs4680 SNP allele A is a risk factor for LID development in Asian PD patients, while GG genotype is a risk factor for LID development in non-Asian PD patients using different genetic models. Conclusion The results of the present meta-analysis support that the COMT Val158Met polymorphism is a risk factor for the development of LID in PD patients having ethnic variations.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association of Catechol-O-Methyltransferase Gene rs4680 Polymorphism and Levodopa Induced Dyskinesia in Parkinson’s Disease: A Meta-Analysis and Systematic Review

Dwivedi

Kumar

et al. 2022

J Geriatr Psychiatry Neurol

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“…Research has shown that individuals with the COMT LL genotype are more susceptible to developing LID due to the genotype's correlation with significant dopaminergic denervation and decreased enzymatic activity. These elements have the potential to interfere with the dopaminergic pathway, causing an accumulation of dopamine in the synaptic cleft, consequently leading to the initiation of LID (Dos Santos et al 2020). Ivanova et al reported that several COMT SNPs related to levodopa, such as rs165774, rs4818, rs4633, and rs4680, among these four SNPs, COMT Val158Met (rs46680) have an influence on the prevalence of LID in Parkinson's disease, but the impact is relatively small.…”

Section: Results and Discussion Pharmacogenomics Of Levodopa Therapymentioning

confidence: 99%

The Relationship Between COMT and MAO-B Gene Polymorphisms with Levodopa in Parkinson’s Disease Patients; A Review

Hasna,

Kasasiah,

Manalu

et al. 2024

JPBN

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Parkinson's disease is a degenerative nervous system disorder caused by the death of dopamine-producing cells in the substantia nigra. Dopaminergic treatment could alleviate motor symptoms for a period. One of the effective dopaminergic medications for symptomatic relief was Levodopa and dopamine agonists. Clinically, Levodopa was always combined with Dopa Decarboxylase (DDC) inhibitors, which redirected Levodopa metabolism towards the COMT pathway, increasing its bioavailability in the central nervous system. The purpose of this article was to investigate the relationship between COMT and MAO-B gene polymorphisms and Levodopa in Parkinson's disease patients, starting by gathering literature on the association between COMT and MAO-B polymorphisms and Levodopa in Parkinson's disease patients using various databases. Reviewed literature revealed that the most frequent polymorphism in the COMT gene was rs4680. Some polymorphisms significantly impacted the treatment of Parkinson's disease patients. However, despite efforts to identify genetic factors influencing the risk of side effects or treatment ineffectiveness, the role of pharmacogenetics in Parkinson's disease has not been fully explored and lacks consistent clinical recommendations. Further research was needed to tailor treatment to individual polymorphisms so that pharmacogenomic approaches could be applied more consistently

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“…Another study in 2020 assessed the impact of variants in several genes on the development of levodopa-induced dyskinesia (LID) in 220 patients with idiopathic PD. COMT LL genotype was seen to increase the chances of developing LID, suggesting that polymorphism in the COMT genotype should be considered before the treatment of LID in PD patients [ 34 ]. Most of the studies of PD focus on the rs4680 variant of the COMT gene.…”

Section: Reviewmentioning

confidence: 99%

Effect of Catechol-O-Methyltransferase Genotype Polymorphism on Neurological and Psychiatric Disorders: Progressing Towards Personalized Medicine

Srivastava¹,

Ochuba²,

Sandhu³

et al. 2021

Cureus

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Different polymorphisms of the catechol-O-methyltransferase (COMT) gene affect the COMT enzyme activity. The COMT enzyme plays a major role in the pathophysiology of various neurological and psychiatric disorders. This review article aims to discuss what recent research has discovered about the association of COMT genotype polymorphism with neurological and psychiatric disorders and the scope for the knowledge to be applied for advancement in therapeutics. We searched PubMed and Google Scholar databases and found 1656 articles. We included observational studies, clinical trials, and meta-analyses in the English language published between 2019 and 2021. We screened the articles based on the title and the abstract and found 26 relevant articles. Diseases or conditions studied primarily were schizophrenia, Parkinson's disease, Alzheimer's disease, substance use, and depression. This article highlights how genetics influences the susceptibility of an individual to neurological and psychiatric diseases and the variations in the specific symptoms of those diseases. The review showed that the variability in individual response to therapeutic interventions stems from the gene level. This knowledge can contribute towards the dawn of a new era of personalized medicine.

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Pharmacogenetic profile and the development of the dyskinesia induced by levodopa-therapy in Parkinson’s disease patients: a population-based cohort study

Cited by 8 publications

References 50 publications

Association of Catechol-O-Methyltransferase Gene rs4680 Polymorphism and Levodopa Induced Dyskinesia in Parkinson’s Disease: A Meta-Analysis and Systematic Review

Association of Catechol-O-Methyltransferase Gene rs4680 Polymorphism and Levodopa Induced Dyskinesia in Parkinson’s Disease: A Meta-Analysis and Systematic Review

The Relationship Between COMT and MAO-B Gene Polymorphisms with Levodopa in Parkinson’s Disease Patients; A Review

Effect of Catechol-O-Methyltransferase Genotype Polymorphism on Neurological and Psychiatric Disorders: Progressing Towards Personalized Medicine

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