Association of Catechol-O-Methyltransferase and monoamine oxidase B gene polymorphisms with motor complications in parkinson's disease in a Chinese population

Hao, Hongying; Shao, Ming; An, Jing; Chen, Chushuang; Feng, Xiaoyan; Xie, Shu; Gu, Zhuqin; Chan, Piu

doi:10.1016/j.parkreldis.2014.06.021

Cited by 31 publications

(26 citation statements)

References 25 publications

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“…MAO-B inhibitors can protect neurons by anti-oxidative stress, inhibiting synuclein aggregation and reducing apoptosis and neurotrophic effects [13, 14]. A COMT inhibitor combined with LD can extend the “on” time and shorten the “off” time [15]. The eleven therapeutic drugs of PD in the study are LD; DA agonists (ropinirole and pramipexole); DA receptor agonists (rotigotine, apomorphine, sumanirole, piribedil and bromocriptine); a COMT inhibitor (entacapone); and a highly active MAO-B inhibitor (rasagiline).…”

Section: Introductionmentioning

confidence: 99%

Comparison of the Efficacy of Different Drugs on Non-Motor Symptoms of Parkinson’s Disease: a Network Meta-Analysis

Li¹,

Cui²,

Song³

et al. 2018

Cell Physiol Biochem

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Background/Aims: A network meta-analysis is used to compare the efficacy of ropinirole, rasagiline, rotigotine, entacapone, apomorphine, pramipexole, sumanirole, bromocriptine, piribedil and levodopa, with placebo as a control, for non-motor symptoms in Parkinson’s disease (PD). Methods: PubMed, Embase and the Cochrane Library were searched from their establishment dates up to January 2017 for randomized controlled trials (RCTs) investigating the efficacy of the above ten drugs on the non-motor symptoms of PD. A network meta-analysis combined the evidence from direct comparisons and indirect comparisons and evaluated the pooled weighted mean difference (WMD) values and surfaces under the cumulative ranking curves (SUCRA). The network meta-analysis included 21 RCTs. Results: The analysis results indicated that, using the United Parkinson’s Disease Rating Scale (UPDRS) III, the efficacies of placebo, ropinirole, rasagiline, rotigotine, entacapone, pramipexole, sumanirole and levodopa in treating PD were lower than that of apomorphine (WMD = -10.90, 95% CI = -16.12∼-5.48; WMD = -11.85, 95% CI = -17.31∼-6.16; WMD = -11.15, 95% CI = -16.64∼-5.04; WMD = -11.70, 95% CI = -16.98∼-5.60; WMD = -11.04, 95% CI = -16.97∼-5.34; WMD = -13.27, 95% CI = -19.22∼-7.40; WMD = -10.25, 95% CI = -15.66∼-4.32; and WMD = -11.60, 95% CI = -17.89∼-5.57, respectively). Treatment with ropinirole, rasagiline, rotigotine, entacapone, pramipexole, sumanirole, bromocriptine, piribedil or levodopa, with placebo as a control, on PD exhibited no significant differences on PD symptoms when the UPDRS II was used for evaluation. Moreover, using the UPDRS III, the SUCRA values indicated that a pomorphine had the best efficacy on the non-motor symptoms of PD (99.0%). Using the UPDRS II, the SUCRA values for ropinirole, rasagiline, rotigotine, entacapone, pramipexole, sumanirole, bromocriptine, piribedil and levodopa treatments, with placebo as a control, indicated that bromocriptine showed the best efficacy on the non-motor symptoms of PD (75.6%). Conclusion: Among ropinirole, rasagiline, rotigotine, entacapone, apomorphine, pramipexole, sumanirole, bromocriptine, piribedil and levodopa, with placebo as a control, apomorphine may be the most efficacious drug for therapy in treating the non-motor symptoms of PD.

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Section: Introductionmentioning

confidence: 99%

Comparison of the Efficacy of Different Drugs on Non-Motor Symptoms of Parkinson’s Disease: a Network Meta-Analysis

Li¹,

Cui²,

Song³

et al. 2018

Cell Physiol Biochem

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“…Bialecka, Kurzawski [1] reported a study of COMT haplotypes in Poland that did not identify a significant impact of COMT haplotypes on the development of the “wearing-off” phenomenon, longer disease duration and larger LED. Hao, Shao [9] found that the rs4680 GG allele may be a risk factor for the “wearing-off” phenomenon. The reasons for the discrepancy with our results may be that the patients involved in our study presented different disease severities.…”

Section: Discussionmentioning

confidence: 99%

“…The COMT protein encoded by the L allele is thermolabile, which influences individual variations in the therapeutic response to levodopa and susceptibility to PD [6–9]. Moreover, studies [1, 10–12] have focused on three other common haplotypes comprising combinations of four SNPs in the COMT gene: rs6269 A > G, rs4633 C > T (His62His), rs4818 C > G (Leu136Leu) and rs4680 G > A (Val158Met).…”

Section: Introductionmentioning

confidence: 99%

Roles of functional catechol-O-methyltransferase genotypes in Chinese patients with Parkinson’s disease

Xiao

Qian

Liu

et al. 2017

Transl Neurodegener

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BackgroundRecent studies have found that the functional catechol-O-methyltransferase (COMT) gene may be associated with the susceptibility to and pharmacotherapy of Parkinson’s disease (PD). In this case–control study, we investigated the most common functional COMT gene haplotypes that had been shown to influence COMT enzymatic activity and the association of the single and combined COMT haplotypes with clinical symptoms and pharmacotherapy in Chinese patients with PD.MethodsOne hundred forty-three patients with idiopathic PD and 157 healthy individuals were enrolled in this study. Four single nucleotide polymorphisms (SNPs) in the COMT gene (formed by SNPs) were genotyped in each participant: rs6269 A > G; rs4633 C > T; rs4818 C > G; and rs4680 G > A.ResultsThe frequencies of rs4633 T carriers, rs4680 A carriers and the two linked rs4633-rs4680 T/A carriers were significantly higher in the early onset PD group than in the healthy controls (all P < 0.05). Homozygosity for rs4633 (TT), rs4680 (AA) and of the two linked rs4633-rs4680 (TT/AA) was significantly more frequent in patients who exhibited the “wearing-off” phenomenon, longer disease duration, higher levodopa equivalent doses (LED) and higher Unified Parkinson’s Disease Rating Scale (UPDRS) scores (P < 0.05). No significant differences were observed in the clinical features of patients who carried individual rs6269 and rs4818, the two linked rs6269-rs4818 and the four combined COMT SNPs.ConclusionsThe results showed a possible association of combined functional COMT SNPs with PD risk, disease duration, the “wearing-off” phenomenon, daily LEDs and higher UPDRS scores, which may be useful in instituting individualized therapy for patients with PD.Electronic supplementary materialThe online version of this article (doi:10.1186/s40035-017-0081-9) contains supplementary material, which is available to authorized users.

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“…Watanabe et al showed that homozygosity for the low-activity allele (AA genotype) increased chances for wearing-off phenomenon (p = 0.047) and dyskinesia (p = 0.045) [46]. On the contrary, a later study found association of the GG genotype with wearing-off phenomenon (p = 0.049 for the GG genotype and 0.031 for the G allele) [47]. The same results were also found in the study by Wu et al [48].…”

Section: Genetic Variability In Dopamine Metabolic Pathway Genes Affementioning

confidence: 98%

“…Carriers of the heterozygous genotype at the MAO-B rs3837091 were found to be more prone to develop dyskinesia [47].…”

Section: Genetic Variability In Dopamine Metabolic Pathway Genes Affementioning

confidence: 99%

Effects of Genetic Variability in Dopaminergic Pathway on Treatment Response in Parkinson’s Disease

Redenšek¹,

Trošt²,

Dolžan³

2018

Parkinson's Disease - Understanding Pathophysiology and Developing Therapeutic Strategies

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Parkinson's disease (PD) is a chronic progressive neurodegenerative brain disorder presenting with motor signs and symptoms, such as akinesia, rest tremor, rigidity, and later in disease progression postural instability. However, nonmotor symptoms may harm patients' quality of life even more than the motor ones. The etiopathogenesis is not clear yet. PD may develop due to a combination of genetic and environmental factors. It is treated symptomatically with dopaminergic drugs. The gold standard of PD management is L-Dopa, however also other drugs are frequently used, such as dopamine agonists, MAOB inhibitors, COMT inhibitors, and occasionally amantadine and anticholinergic drugs. Many patients experience several adverse events of L-Dopa treatment, such as different motor complications. Furthermore, nonmotor adverse events of dopaminergic treatment may occur. The efficacy of drugs varies between patients as well. Several polymorphic genes have already been associated with treatment outcome in PD, such as metabolic enzymes, transport and receptor genes, and might serve as treatment outcome prediction factors. As gene-environment interactions were also shown to contribute to PD development, they might also be able to predict treatment response. Such genetic biomarkers could be helpful in personalized care of PD patients to prevent adverse events and inefficacy of a certain drug.

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Association of Catechol-O-Methyltransferase and monoamine oxidase B gene polymorphisms with motor complications in parkinson's disease in a Chinese population

Cited by 31 publications

References 25 publications

Comparison of the Efficacy of Different Drugs on Non-Motor Symptoms of Parkinson’s Disease: a Network Meta-Analysis

Comparison of the Efficacy of Different Drugs on Non-Motor Symptoms of Parkinson’s Disease: a Network Meta-Analysis

Roles of functional catechol-O-methyltransferase genotypes in Chinese patients with Parkinson’s disease

Effects of Genetic Variability in Dopaminergic Pathway on Treatment Response in Parkinson’s Disease

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