Nonsynonymous Polymorphisms of Histamine-Metabolising Enzymes in Patients with Parkinson’s Disease

Abstract

To analyze genetically based impairment in histamine-metabolising enzymes in patients with Parkinson's disease (PD). 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. An association of the HNMT Thr105Ile 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). 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.