Nonsynonymous polymorphisms of histamine-metabolising enzymes in patients with Parkinson's disease
Nonsynonymous polymorphisms of histamine-metabolising enzymes in patients with Parkinson's disease
复制标题
DOI：
10.1007/s12017-007-8017-7
复制
发表时间：
2008-01-01
影响因子：
3.5
通讯作者：
Garcia-Martin, Elena
中科院分区：
文献类型：
--
作者：
Agundez, Jose A. G.;Luengo, Antonio;Garcia-Martin, Elena
目的分析帕金森病（PD）患者组胺代谢酶的基因缺陷。方法采用扩增限制性分析方法，对214例PD患者和295例无亲缘关系健康对照者的白细胞DNA进行非同义组胺n-甲基转移酶（HNMT）和二胺氧化酶（ABP1）多态性研究。结果HNMT Thr-105Ile多态性与PD相关，而ABP1 His645Asp多态性与PD无关。与健康受试者相比，PD患者表现出更高频率的纯合子HNMT基因型，导致高活性的基因剂量效应（P < 0.001）。这些发现与性别无关，但在迟发性PD患者中，与HNMT多态性的相关性更高（P < 0.0001）。这些结果，结合先前PD患者组胺水平改变的研究结果，提示SNC组胺稳态的改变与PD的风险相关。
Objective To analyze genetically based impairment in histamine-metabolising enzymes in patients with Parkinson's disease (PD). Methods Leukocytary DNA from 214 PD patients and a control group of 295 unrelated healthy individuals was studied for nonsynonymous histamine N-methyltransferase (HNMT) and diamine oxidase (ABP1) polymorphisms by using amplification-restriction analyses. Results An association of the HNMT Thr-105Ile polymorphism, but not of the ABP1 His645Asp polymorphism, with PD was observed. Patients with PD showed a higher frequency of homozygous HNMT genotypes leading to high activity with a gene-dose effect (P < 0.001), as compared to healthy subjects. These findings were independent of gender, but the association with the HNMT polymorphism is higher among patients with late-onset PD (P < 0.0001). Conclusion These results, combined with previous findings indicating alterations in histamine levels in patients with PD, suggest that alterations of histamine homeostasis in the SNC are associated with the risk for PD.