Thr105Ile (rs11558538) polymorphism in the histamine N-methyltransferase (HNMT) gene and risk for Parkinson disease A PRISMA-compliant systematic review and meta-analysis
MEDICINE
Authors: Javier Jimenez-Jimenez, Felix; Alonso-Navarro, Hortensia; Garcia-Martin, Elena; Agundez, Jose A. G.
Abstract
Background/aims: Several neuropathological, biochemical, and pharmacological data suggested a possible role of histamine in the etiopathogenesis of Parkinson disease (PD). The single nucleotide polymorphism (SNP) rs11558538 in the histamine N-methyltransferase (HNMT) gene has been associated with the risk of developing PD by several studies but not by some others. We carried out a systematic review that included all the studies published on PD risk related to the rs11558538 SNP, and we conducted a meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Methods: We used several databases to perform the systematic review, the software Meta-DiSc 1.1.1 to perform the meta-analysis of the eligible studies, and the Q-statistic to test heterogeneity between studies. Results: The meta-analysis included 4 eligible case-control association studies for the HNMT rs11558538 SNP and the risk for PD (2108 patients, 2158 controls). The frequency of the minor allele positivity showed a statistically significant association with a decreased risk for PD, both in the total series and in Caucasians. Although homozygosity for the minor allele did not reach statistical significance, the test for trend indicates the occurrence of a gene-dose effect. Global diagnostic odds ratios (95% confidence intervals) for rs11558538T were 0.61 (0.46-0.81) for the total group, and 0.63 (0.45-0.88) for Caucasian patients. Conclusion: The present meta-analysis confirms published evidence suggesting that the HNMT rs11558538 minor allele is related to a reduced risk of developing PD.
Optically active iodohelicene derivatives exhibit histamine N-methyl transferase inhibitory activity
JOURNAL OF ANTIBIOTICS
Authors: Ichinose, Wataru; Sawato, Tsukasa; Kitano, Haruna; Shinozaki, Yasuhiro; Arisawa, Mieko; Saito, Nozomi; Yoshikawa, Takeo; Yamaguchi, Masahiko
Abstract
Optically active helicene derivatives inhibit the activity on histamine N-methyl transferase (HNMT). Specifically, methyl (P)-1,12-dimethylbenzoMphenanthrene-8-carboxylate with 6-iodo and 5-trifluoromethanesulfonyloxy groups inhibits HNMT activity on the mu M order of IC50. Chirality is important, and (M)-isomers exhibits substantially reduced activity. The 6-iodo group is also essential, which suggests the involvement of halogen bonds in protein binding. Substituents on the sulfonate moiety also affect the inhibitory activity.