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

Abstract

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.

The Nonsynonymous Thr105Ile Polymorphism of the Histamine N-Methyltransferase is Associated to the Risk of Developing Essential Tremor

“…In contrast to previous studies that have focused on enzymes related to xenobiotic metabolism (Agundez et al 1997;Alonso-Navarro et al 2006;Martinez et al 2007), this study focuses on an enzyme involved in the degradation of endogenous substances. Several studies support a role of histamine in PD (Coelho et al 1991;Prell and Green 1991;Langlais et al 1994;Thoburn et al 1994;Anichtchik et al 2000;Agundez et al 2007), but this is the first study that provides hypothesis-generating data arguing for a role of histamine in ET, and raises the question of whether other movement disorders besides ET and PD could be related to genetic alterations of histamine metabolism.…”

Hypersensitivity Reactions to Non-Steroidal Anti-Inflammatory Drugs

“…The 939A>G polymorphism in patients with AICU is responsible for a reduction in Nmethyltransferase enzymatic activity because this SNP affects mRNA stability, leading to an increase in the levels of diamine [133]. Other clinical implications for histamine-metabolizing enzymes and for variability in histamine receptors are described elsewhere [136,[139][140][141][142].…”

Modulation of behavior by the histaminergic system: Lessons from HDC-, H3R- and H4R-deficient mice

“…Histamine is taken up through OCT3 (organic cation transporter)-or PMAT (plasma membrane monoamine transporter) and then inactivated by cytosolic HNMT (Yoshikawa et al, 2013). Since the Thr105Ile polymorphism was reported to be associated with PD (Agúndez et al, 2008;Palada et al, 2012) or with alcoholism and anxiety (Oroszi et al, 2005), it would be interesting to investigate the behavioral phenotype of HNMT-deficient mice. Specifically, a direct comparison of HNMT-deficient mice and Hrh3 −/− mice should be performed, because both strains represent different mechanisms that result in enhanced histaminergic stimulation and corresponding compensatory processes.…”

“…Moreover, in situ hybridization revealed increased H 3 R mRNA expression in the globus pallidus externus of PD patients (Anichtchik et al, 2001). Interestingly, the Thr105Ile polymorphism of histamine-N-methyltransferase (HNMT), which results in reduced histamine inactivation, was positively correlated with PD in two studies with European patient samples (Agúndez et al, 2008;Palada et al, 2012), but not with North American patients (Keeling et al, 2010). H 3 R density was increased on the protein level in PD substantia nigra ([ 3 H]-N-␣-methyl histamine binding) (Anichtchik et al, 2001), while a later study showed decreased expression of H 3 R mRNA in the substantia nigra of PD patients (Shan et al, 2012a).…”