Nonsynonymous polymorphisms of histamine-metabolising enzymes in patients with Parkinson's disease

被引：33

作者：

Agundez, Jose A. G. ^{[2
]}

Luengo, Antonio ^{[3
]}

Herraez, Oscar ^{[2
]}

Martinez, Carmen ^{[2
]}

Alonso-Navarro, Hortensia ^{[4
]}

Jimenez-Jimenez, Felix Javier ^{[4
]}

Garcia-Martin, Elena ^{[1
]}

机构：

[1] Univ Extremadura, Dept Biochem & Mol Biol, Sch Biol Sci, E-06071 Badajoz, Spain

[2] Univ Extremadura, Dept Pharmacol & Psychiat, Sch Med, Badajoz, Spain

[3] Univ Hosp Princesa, Serv Neurol, Madrid, Spain

[4] Univ Alcala de Henares, Dept Med Neurol, Principe Asturias Hosp, Madrid, Spain

来源：

NEUROMOLECULAR MEDICINE | 2008年 / 10卷 / 01期

关键词：

Parkinson's disease; histamine; HNMT; DAO; ABP1;

D O I：

10.1007/s12017-007-8017-7

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：10 / 16

页数：7

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