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细胞色素P-450IID6基因多态性与散发性特发性帕金森病之间无关联。

Lack of relation between genetic polymorphism of cytochrome P-450IID6 and sporadic idiopathic Parkinson's disease.

作者信息

Bordet R, Broly F, Destée A, Libersa C, Lafitte J J

机构信息

Service de Neurologie A, CH, Lille, France.

出版信息

Clin Neuropharmacol. 1996 Jun;19(3):213-21. doi: 10.1097/00002826-199619030-00003.

Abstract

We investigated genetic polymorphism of the cytochrome P-450 CYP2D6 gene from white patients with idiopathic Parkinson's disease (IPD). The mutations of the CYP2D6 gene associated with the poor metabolizer (PM) phenotype of the debrisoquine/sparteine polymorphism were analyzed in DNA of 130 IPD patients by a polymerase chain reaction (PCR)-based DNA amplification combined with Xba I restriction fragment length polymorphism (RFLP) analysis in 105 patients. Another mutation located in exon 6 was analyzed by Hha I RFLP in 94 IPD patients. The frequencies of the different CYP2D6 gene mutations were compared to the frequencies in sex- and age-matched white control population with chronic bronchitis. The rate of genotypically defined PM and the frequencies of the different mutations were not significantly different in IPD patients and controls. These results fail to confirm the previously reported results concerning CYP2D6 gene mutations in IPD. These equivocal results might be related to methodologic problems. However, other hypotheses have been suggested: impairment of neuronal CYP 2D6 expression, transient modification of CYP 2D6 phenotype, or linkage of CYP2D6 gene to the candidate gene locus directly involved in IPD.

摘要

我们研究了特发性帕金森病(IPD)白人患者细胞色素P - 450 CYP2D6基因的遗传多态性。通过聚合酶链反应(PCR)- 基于DNA扩增结合Xba I限制性片段长度多态性(RFLP)分析,在105例IPD患者的DNA中分析了与异喹胍/司巴丁多态性的慢代谢者(PM)表型相关的CYP2D6基因突变。通过Hha I RFLP在94例IPD患者中分析了位于外显子6的另一个突变。将不同CYP2D6基因突变的频率与患有慢性支气管炎的性别和年龄匹配的白人对照人群中的频率进行比较。IPD患者和对照组中基因分型定义的PM率和不同突变的频率没有显著差异。这些结果未能证实先前报道的关于IPD中CYP2D6基因突变的结果。这些模棱两可的结果可能与方法学问题有关。然而,也提出了其他假设:神经元CYP 2D6表达受损、CYP 2D6表型的短暂改变或CYP2D6基因与直接参与IPD的候选基因位点的连锁。

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