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Polymorphisms of histamine-metabolizing enzymes and clinical manifestations of asthma and allergic rhinitis


Prof. José A. G. Agúndez, Department of Pharmacology, Medical School, University of Extremadura, Avda de Elvas s/n, E-06071, Badajoz, Spain.


Background Polymorphisms of enzymes involved in histamine biodisposition may affect clinical symptoms in diseases related to histamine, such as asthma or allergic rhinitis (AR).

Objective This study aims to analyse two common polymorphisms in genes coding for histamine-metabolizing enzymes in patients with allergic diseases.

Methods 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.

Results 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.

Conclusion 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.

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