Anti-HNMT monoclonal antibody, clone 3H23

Several abnormalities, including lower histamine levels in brain, elevated serum histamine and degeneration of histaminergic neurons in tuberomammillary nucleus, were described in the histaminergic system of patients with Alzheimer's disease (AD). Histamine is a central neurotransmitter with several functions in brain including regulation of memory, cognition, locomotion, and is degraded in part by histamine N-methyltransferase (HNMT). A common Thr105Ile polymorphism within HNMT gene results in decreased enzyme activity. The Thr105Ile polymorphism was associated with Parkinson's disease, essential tremor, attention-deficit hyperactivity disorder (ADHD), asthma and alcoholism, thus we tested possible association of HNMT functional polymorphism with AD. We have tested 256 AD cases and 1190 healthy controls of Croatian origin. Thr105Ile polymorphism was determined by TaqMan RT-PCR Genotyping Assay and EcoRV digestion. Prevalence of functional HNMT polymorphism among all tested groups was similar and frequency of less active Ile105 variant was 11.5% among AD patients and 13.4% for healthy controls (p = 0.26, X-2 = 1.25). Our results indicate lack of the association of HNMT Thr105Ile functional polymorphism with Alzheimer's disease. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Background: Histamine N-methyltransferase (HNMT) plays an important role in the metabolism of histamine, a biogenic amine that has many physiologic and pathological roles in human tissues. A missense mutation C314T (Thr105Ile) in the HNMT gene has been identified to represent a common functional polymorphism in Caucasians, whereas an A595G (Ile199Val) variant has been reported in one HNMT cDNA from a Japanese subject. Methods: By using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay, the point mutations C314T and A595G within HNMT were both detected in 352 unrelated Chinese Han subjects. Results: None of the 352 subjects contained the A595G mutation, whereas 40 (11.6%) heterozygotes and 1 (0.3%) homozygote for the variant T314 allele were detected. The frequency of the variant T314 allele in this Chinese population was 0.060 (95% CI: 0.042-0.078), not different from Japanese but significantly lower than American Caucasians. Conclusions: The C314T mutation represents a common functional genetic polymorphism in the Chinese Han population with a variant T314 allele frequency similar to Japanese but lower than American Caucasians, whereas the A595G mutation does not appear to exist in this population. (C) 2002 Elsevier Science B.V. All rights reserved.