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伊朗散发性帕金森病患者中儿茶酚-O-甲基转移酶和单胺氧化酶B基因多态性与左旋多巴治疗

The catechol-O-methyltransferase and monoamine oxidase B polymorphisms and levodopa therapy in the Iranian patients with sporadic Parkinson's disease.

作者信息

Torkaman-Boutorabi Anahita, Shahidi Gholam Ali, Choopani Samira, Rezvani Mohammad, Pourkosary Kosar, Golkar Majid, Zarrindast Mohammad-Reza

机构信息

Department of Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran.

出版信息

Acta Neurobiol Exp (Wars). 2012;72(3):272-82. doi: 10.55782/ane-2012-1900.

DOI:10.55782/ane-2012-1900
PMID:23093014
Abstract

Parkinson's disease (PD) patients vary widely in their response to levodopa treatment, and this may be partially genetic in origin. Recent studies suggest that catechol-O-methyltransferase (COMT), G1947A and monoamine oxidase B (MAOB), A644G polymorphisms might influence the risk and treatment of PD. Herein, we aimed to test the possible influence of MAOB and COMT genetic polymorphisms on the effective daily dose of levodopa administered in the fifth year of treatment. We also examined the effect of COMT and MAOB haplotypes on levodopa therapy outcome. There were 31 females and 72 males of Iranian origin diagnosed with sporadic PD included into the study. The patients were divided into two groups. Group 1: patients received daily doses of levodopa below 500 mg in the fifth year of treatment. Group 2: those patients receiving daily doses exceeding 500 mg in the fifth year of treatment. MAOB and COMT polymorphism genotyping was performed by using PCR-based restriction fragment length polymorphism (RFLP) analyses. Our data show that the first group suffered less frequently from dyskinesia than patients from the second group. No statistically significant differences were found in allele frequencies and genotype distributions of the studied genes between two groups. In addition, the incidence of the specific haplotypes between the two groups did not show any difference. The present data suggest that pharmacokinetic or pharmacodynamic factors other than the investigated genetic variants of the MAOB and COMT enzymes seem to determine the response to levodopa in the Iranian PD patients.

摘要

帕金森病(PD)患者对左旋多巴治疗的反应差异很大,这可能部分源于遗传因素。最近的研究表明,儿茶酚-O-甲基转移酶(COMT)基因G1947A多态性和单胺氧化酶B(MAOB)基因A644G多态性可能会影响PD的发病风险和治疗效果。在此,我们旨在测试MAOB和COMT基因多态性对治疗第5年时左旋多巴每日有效剂量的可能影响。我们还研究了COMT和MAOB单倍型对左旋多巴治疗效果的影响。本研究纳入了31名伊朗裔女性和72名伊朗裔男性,他们均被诊断为散发性PD。患者被分为两组。第1组:治疗第5年时每日接受左旋多巴剂量低于500 mg的患者。第2组:治疗第5年时每日接受左旋多巴剂量超过500 mg的患者。采用基于聚合酶链反应(PCR)的限制性片段长度多态性(RFLP)分析方法对MAOB和COMT基因多态性进行基因分型。我们的数据显示,第1组患者出现运动障碍的频率低于第2组患者。两组之间所研究基因的等位基因频率和基因型分布未发现统计学上的显著差异。此外,两组之间特定单倍型的发生率也没有差异。目前的数据表明,除了所研究的MAOB和COMT酶的基因变异外,其他药代动力学或药效学因素似乎决定了伊朗PD患者对左旋多巴的反应。

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Molecular Mechanisms and Therapeutic Strategies for Levodopa-Induced Dyskinesia in Parkinson's Disease: A Perspective Through Preclinical and Clinical Evidence.
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