Histamine N-methyltransferase (HNMT) pharmacogenetics: Association of the C314T genetic polymorphism with allergic asthma

Asthma is an important public health problem that affects an estimated 150 million individuals worldwide. HNMT plays a dominant role in histamine biotransformation in bronchial epithelium. We have described a C314T polymorphism within the HNMT gene that results in a Thr105I1e change in encoded amino acid as well as decreased HNMT activity. We set out to determine whether this common genetic polymorphism might represent a risk factor for asthma. 63 asthmatic patients as well as 237 randomly selected blood donors were genotyped for the C314T polymorphism. The T314 variant allele was more common in patients with asthma than in control subjects (allele frequencies 0.19 vs 0.08, χ² = 12.40, p = 0.001, odds ratio = 2.62). These differences were accentuated when only patients with allergic asthma were included in the analysis (allele frequency = 0.21, χ² = 15.13, p = 0.001, odds ratio = 2.95). These data suggest that inherited variation in histamine metabolism might be one factor involved in the pathophysiology and pharmacogenetics of asthma - particularly in patients who suffer from atopy.