Histamine N-methyltransferase pharmacogenetics: association of a common functional polymorphism with asthma

Histamine is involved in the pathophysiology of asthma, and histamine N-met hyltransferase (HNMT) plays the dominant role in histamine metabolism in hu man bronchial epithelium, Levels of HNMT activity in human tissues are cont rolled, in part, by inheritance. A common C314T polymorphism within the HNM T gene results in a Thr105Ile change in encoded amino acid, and the T314 al lele is associated with decreased levels of both HNMT enzymatic activity an d immunoreactive protein. Therefore, presence of the T314 allele would be e xpected to result in reduced histamine metabolism and increased bronchocons triction. We characterized this common, functionally significant polymorphi sm in DNA samples from 237 randomly selected Caucasian control subjects and 192 samples from Caucasian asthmatic patients. Allele frequencies for the T314 HNMT allele were 0.08 in the control samples and 0.14 in samples from Caucasian asthmatic patients (odds ratio = 1.9, P < 0.01), indicating a sig nificant increase in the frequency of subjects with low HNMT activity among asthmatics. The association between a common, functionally significant gen etic polymorphism for HNMT and asthma suggests that individual variation in histamine metabolism might contribute to the pathophysiology and/or respon se to therapy of this disease. Pharmacogenetics 10:261-266 (C) 2000 Lippinc ott Williams & Wilkins.