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帕金森病患者的多巴胺转运体基因多态性、单光子发射计算机断层扫描成像及左旋多巴反应

Dopamine transporter gene polymorphism, spect imaging, and levodopa response in patients with Parkinson disease.

作者信息

Contin Manuela, Martinelli Paolo, Mochi Mirella, Albani Fiorenzo, Riva Roberto, Scaglione Cesa, Dondi Maurizio, Fanti Stefano, Pettinato Cinzia, Baruzzi Agostino

机构信息

Neurology Clinic, Department of Neurological Sciences, University of Bologna, Italy.

出版信息

Clin Neuropharmacol. 2004 May-Jun;27(3):111-5. doi: 10.1097/00002826-200405000-00004.

Abstract

OBJECTIVES

To assess the potential association between dopamine transporter (DAT) genotype, single photon emission CT (SPECT) measures using [123I]-N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl)nortropane ([123I]-FP-CIT) of striatal dopaminergic function, and oral levodopa response pattern in a cohort of patients with Parkinson disease.

METHODS

Thirty-six patients at different disease stages enrolled in the study. Each patient was examined by [123I]-FP-CIT SPECT and a standardized oral levodopa test on 2 separate days in a randomized order within 3 weeks. The main outcome variables were the specific-to-nonspecific tracer uptake ratio in the contralateral putamen for SPECT analysis; latency, duration, and magnitude of the motor effect; and presence of dyskinesias for the levodopa test. The variable number of tandem repeat (VNTR) polymorphisms of the gene coding for DAT were detected for each patient by standard methods.

RESULTS

Contralateral putamen [123I]-FP-CIT uptake ratios were similar in the patients carrying the 9-copy allele (n=20) of the DAT VNTR compared with 10-repeat homozygotes (n=16). No significant difference was found in levodopa main outcome variables and dyskinesia incidence between the two groups of patients stratified by DAT VNTR polymorphism.

CONCLUSIONS

The study did not identify clinically relevant in vivo DAT neurochemical function phenotypes or levodopa response patterns associated with the DAT polymorphism.

摘要

目的

评估帕金森病患者队列中多巴胺转运体(DAT)基因型、使用[123I]-N-ω-氟丙基-2β-甲氧基羰基-3β-(4-碘苯基)去甲托烷([123I]-FP-CIT)进行的单光子发射计算机断层扫描(SPECT)测量的纹状体多巴胺能功能与口服左旋多巴反应模式之间的潜在关联。

方法

36名处于不同疾病阶段的患者参与了该研究。每位患者在3周内以随机顺序在2个不同日期接受[123I]-FP-CIT SPECT检查和标准化口服左旋多巴试验。主要结局变量包括用于SPECT分析的对侧壳核中特异性与非特异性示踪剂摄取率;运动效应的潜伏期、持续时间和幅度;以及左旋多巴试验中异动症的存在情况。通过标准方法检测每位患者编码DAT的基因的可变串联重复(VNTR)多态性。

结果

与10次重复纯合子(n = 16)相比,携带DAT VNTR 9拷贝等位基因(n = 20)的患者对侧壳核[123I]-FP-CIT摄取率相似。在按DAT VNTR多态性分层的两组患者之间,左旋多巴主要结局变量和异动症发生率未发现显著差异。

结论

该研究未发现与DAT多态性相关的具有临床相关性的体内DAT神经化学功能表型或左旋多巴反应模式。

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