Thr105Ile (rs11558538) polymorphism in the histamine-1-methyl-transferase (HNMT) gene and risk for restless legs syndrome
JOURNAL OF NEURAL TRANSMISSION
Authors: Javier Jimenez-Jimenez, Felix; Garcia-Martin, Elena; Alonso-Navarro, Hortensia; Martinez, Carmen; Zurdo, Martin; Turpin-Fenoll, Laura; Millan-Pascual, Jorge; Adeva-Bartolome, Teresa; Cubo, Esther; Navacerrada, Francisco; Rojo-Sebastian, Ana; Rubio, Lluisa; Ortega-Cubero, Sara; Pastor, Pau; Calleja, Marisol; Francisco Plaza-Nieto, Jose; Pilo-de-la-Fuente, Belen; Arroyo-Solera, Margarita; Garcia-Albea, Esteban; Agundez, Jose A. G.
Abstract
A recent meta-analysis suggests an association between the rs11558538 single nucleotide polymorphism in the histamine-N-methyl-transferase (HNMT) gene and the risk for Parkinson's disease. Based on the possible relationship between PD and restless legs syndrome (RLS), we tried to establish whether rs11558538 SNP is associated with the risk for RLS. We studied the genotype and allelic variant frequencies of HNMT rs11558538 SNP 205 RLS patients and 410 healthy controls using a TaqMan assay. The frequencies of the HNMT rs11558538 genotypes allelic variants were similar between RLS patients and controls, and were not influenced by gender, family history of RLS, or RLS severity. RLS patients carrying the genotype rs11558538TT had an earlier age at onset, but this finding was based on three subjects only. These results suggest a lack of major association between HNMT rs11558538 SNP and the risk for RLS.
Polymorphisms of histamine-metabolizing enzymes and clinical manifestations of asthma and allergic rhinitis
CLINICAL AND EXPERIMENTAL ALLERGY
Authors: Garcia-Martin, E.; Garcia-Menaya, J.; Sanchez, B.; Martinez, C.; Rosendo, R.; Agundez, J. A. G.
Abstract
Polymorphisms of enzymes involved in histamine biodisposition may affect clinical symptoms in diseases related to histamine, such as asthma or allergic rhinitis (AR). This study aims to analyse two common polymorphisms in genes coding for histamine-metabolizing enzymes in patients with allergic diseases. Five-hundred and sixty-five individuals participated in the study, including 270 unrelated patients with asthma and/or AR recruited from a single centre and 295 healthy volunteers. Participants were analysed for the presence of Thr105Ile and His645Asp amino acid substitutions at histamine N-methyltransferase (HNMT) and diamine oxidase (amiloride binding protein 1) enzymes, respectively, by amplification-restriction procedures. The variant HNMT allele frequencies were slightly higher among patients with asthma [16.0%, 95% confidence interval (CI) 12.0-20.0] and among patients with rhinitis (13.2, 95% CI 10.3-16.1) as compared with healthy subjects (11.5 95% CI 8.9-14.1). The variant ABP1 allele frequencies were similar among patients with asthma (30.8%, 95% CI 25.7-35.9), rhinitis (28.7, 95% CI 24.8-32.6) and healthy subjects (26.8 95% CI 23.2-30.3). Individuals carrying mutated ABP1 alleles presented allergy symptoms with significantly lower IgE levels as compared with individuals without mutated genes, with a significant gene-dose effect (P < 0.001). In addition, the percentage of individuals presenting symptoms without eosinophilia was significantly higher among homozygous carriers of ABP1 variant alleles (P < 0.020) as compared with the rest of the atopic patients. There is a lack of association between the allelic variants studied and the risk of developing allergic asthma and rhinitis. However, patients carrying the His645Asp polymorphism of ABP1 are more prone to developing symptoms with lower IgE levels.