Asociación de polimorfismos de diaminoxidasa e histamina N metiltransferasa con la presencia, discapacidad y severidad de migraña en un grupo de madres mexicanas de niños alérgicos / Association of diamine oxidase and histamine N-methyltransferase polymorphisms with presence of migraine in a group of Mexican mothers of children with allergies

Introducción: Se ha sugerido que una degradación disminuida de histamina puede contribuir en la patogénesis de migraña y alergia. Este trabajo investiga una posible asociación entre 2 polimorfismos de un solo nucleótido (SNP) de 2 enzimas que degradan histamina, C314T para la histamina N-metil-transferasa (HNMT) y C2029G para diaminoxidasa (DAO), con la presencia, discapacidad y severidad de la migraña. Material y métodos: Se reclutó a 162 madres de niños alérgicos (80 con migraña y 82 sin migraña) determinando las variantes alélicas por PRC tiempo real usando un modelo de casos y controles. Mediante regresión logística se determinaron las OR para los genotipos y haplotipos. Resultados: El alelo mutado G para DAO fue significativamente más frecuente en el grupo de mujeres migrañosas que en los controles (OR = 1,6; IC del 95% = 1,1-2,1). No encontramos diferencias significativas para el alelo mutado T de la HNMT. Ambos alelos mutados estuvieron asociados a la discapacidad causada por la migraña. La coexistencia de ambas mutaciones (haplotipos) mostró una fuerte asociación con migraña. Los haplotipos que tenían ambos alelos mutados (ya sea como homocigotos o heterocigotos) estuvieron fuertemente asociados a la discapacidad por migraña grado iv (OR = 45,0, IC del 95% = 5,2-358). Esto sugiere que los alelos mutados T para HNMT y G para DAO pueden interactuar incrementando el riesgo y el impacto de la migraña. Conclusiones: Se sugiere una asociación sinérgica de polimorfismos de HNMT y DAO con migraña el cual debe ser confirmado en futuros estudios. La interpretación debe tomar en cuenta las características étnicas de la población estudiada (AU)

Background: Low histamine metabolism has been suggested to play a role in the pathogenesis of allergy and migraine. We investigated the possible association between 2 single-nucleotide polymorphisms (SNP), C314 T HNMT and C2029G DAO, and the presence and severity of migraine and migraine-related disability. Materials and methods: We studied the frequency of C314 T HNMT and C2029G DAO allelic variants in 162 mothers of children with allergies (80 with migraine and 82 without) using a TaqMan-based qPCR Assay and a case-control model. We conducted a logistic regression analysis to examine the association between migraine and the allelic and haplotype variants. Results: Mutant C2029G DAO SNP was found significantly more frequently in the group of women with migraine than in controls (OR, 1.6; 95% CI, 1.1–2.1). No significant differences were found in frequencies of genotypes or alleles in the case of C314T HNMT SNP. Both mutated alleles were associated with migraine-related disability. Coexistence of alleles for both SNPs (haplotypes) showed a strong association with migraine. Haplotypes containing both mutated alleles (either heterozygous or homozygous) were very strongly associated with MIDAS grade iv migraine (OR, 45.0; 95% CI, 5.2-358). This suggests that mutant alleles of C314 T for HNMT and C2029G for DAO polymorphisms may interact in a way that increases the risk and impact of migraine. Conclusions: We suggest a synergistic association between HNMT and DAO functional polymorphisms and migraine; this hypothesis must be further confirmed by larger studies. However, the characteristics and ethnic differences between analysed populations should be considered when interpreting the results (AU)

Association between two polymorphisms of histamine-metabolising enzymes and the severity of allergic rhinitis in a group of Mexican children

BACKGROUND: It has been suggested that polymorphisms of histamine metabolising enzymes can be a risk factor for developing histamine-involving diseases. The aim of the present study is to research the possible association between two functional single nucleotide polymorphisms (SNPs): C314T in the Histamine-N-Methyl Transferase gene and C2029G in the Diamine Oxidase gene, with the severity of allergic rhinitis and the number of allergic diseases, in a group of allergic Mexican children. METHODS: We studied 154 unrelated allergic children. SNPs were analysed by RT-PCR. The total serum IgE was measured by chemiluminescence and the serum histamine by ELISA. We used logistic regression analysis to determine OR. RESULTS: Patients carrying the mutant allele for any SNP had more risk to develop higher rhinitis severity or a bigger number of allergic diseases. Haplotype analysis revealed that this effect is synergistic. In patients carrying one or two mutant alleles, serum histamine levels were higher than those of patients carrying only wild alleles. Serum IgE levels were not associated with the presence of mutant alleles. CONCLUSION: The presence of these SNPs in patients with allergic rhinitis can lead to higher serum histamine, therefore to a higher risk of developing more severe symptoms or more associated allergic diseases, even if the serum IgE remains low

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Influence of iodinated contrast media on the activities of histamine inactivating enzymes diamine oxidase and histamine N-methyltransferase in vitro

BACKGROUND: Iodinated contrast media can cause pseudoallergic reactions associated with histamine release in significant numbers of patients. To clarify whether these adverse reactions may be aggravated by a compromised histamine catabolism we asked if radiographic contrast agents in vitro inhibit the histamine inactivating enzymes diamine oxidase (DAO) and histamine N-methyltransferase (HMT). METHODS: Nine iodinated contrast agents were tested in vitro. Following pre-incubation of purified porcine kidney DAO and recombinant human HMT with 0.1-10 mM of the respective contrast medium (H2O and specific inhibitors of DAO and HMT as controls) enzyme activities were determined by using radiometric micro assays. RESULTS: None of the contrast media irrespective of their structure showed significant inhibition of the activities of DAO and HMT. Pre-incubation of the enzymes with specific inhibitors led to complete inhibition of the respective enzymatic activity. CONCLUSIONS: The iodinated contrast media tested in vitro did not exhibit inhibition of histamine converting enzymes at physiologically relevant concentrations. However due to the in vitro character of this study these results do not directly reflect the in vivo situation

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