Association of Histamine N-Methyltransferase Thr105Ile Polymorphism with Parkinson’s Disease and Schizophrenia in Han Chinese: A Case-Control Study

Abstract

Parkinson’s disease (PD) and schizophrenia (SCZ) are frequent central nervous disorders that have unclear etiologies but that show similarities in their pathogenesis. Since elevated histamine levels in the brain have been associated with PD and SCZ, we wanted to explore whether the Thr105Ile substitution in the histamine N-methyltransferase gene (HNMT-Thr105Ile), which impairs histamine degradation, is associated with either disease. We used the ligase detection reaction to genotype a case-control cohort of Han Chinese patients with PD or SCZ and healthy controls at the HNMT-Thr105Ile locus. The Ile allele was associated with reduced risk of PD (OR 0.516, 95%CI 0.318 to 0.838, p = 0.007) and of SCZ (OR 0.499, 95%CI 0.288 to 0.865, p = 0.011). Genotype frequencies and minor allele frequencies were similar between patients and controls when we compared males with females or early-onset patients with late-onset ones. Genotype and allele frequencies were not significantly different between PD patients with dyskinesia and PD patients without dyskinesia. Our results suggest that the heterozygous Thr/Ile genotype at the HNMT-Thr105Ile locus and the minor Ile105 allele protect against PD and SCZ in Han Chinese.

Histamine H3 receptor as a potential target for cognitive symptoms in neuropsychiatric diseases

“…histamine N-methyltransferase (HNMT) and histidine decarboxylase (HDC), as well as histamine receptors account for inter-individual discrepancy in histamine metabolism and function associated with diverse diseases including neuropsychiatric disorders including AD, epilepsy and SCH [178][179][180][181][182], but that is beyond the scope of this overview.…”

Thr105Ile (rs11558538) polymorphism in the histamine N-methyltransferase (HNMT) gene and risk for Parkinson disease

“…The search using these databases showed 6 case–control association studies on rs11558538 SNPs in the HNMT gene and the risk for PD. [ 25 – 30 ] However, we excluded from the review and meta-analyses 2 studies included in the PD Gene Data Base because the genotype and allele frequencies of the analyzed SNP were not available in the respective reports. [ 26 , 27 ] Therefore, only 4 case–control studies were included in the final meta-analysis.…”

Emerging Concepts of Specific Components of the Immune System in Schizophrenia

“…Histamine may demonstrate pleomorphic actions by acting as a neurotransmitter and as a component of inflammation. Yang et al (18) suggested that dysregulation in histamine (not just dopamine) may play a causative role in schizophrenia. Moreover, histamine is already highly recognized in the pathogenesis and physiology of neurodegenerative diseases.…”

“…Several brain disorders (such as Alzheimer's disease, schizophrenia, Parkinson's disease, and sleep disorders) have been associated with alterations in histamine (16). Interestingly, elevated histamine levels in the blood have been associated with schizophrenia (18). It has been observed that patients with schizophrenia are more tolerant to histamine levels, which may be attributed to an abnormality in histamine metabolism (19).…”

“…Postmortem studies have shown that the density of histamine H1 receptors in the frontal cortex is lower in patients with schizophrenia compared with healthy control subjects (18), possibly due to down-regulation. Vohora and Bhowmik (20) suggested that H3 receptors take part in modulation of cognition, which is impaired in individuals with schizophrenia with psychotic symptoms (20).…”