HistamineN-methyltransferase pharmacogenetics: association of a common functional polymorphism with asthma
作者:
Lan Yan,
Raymond Galinsky,
Jonathan Bernstein,
Stephen Liggett,
Richard Weinshilboum,
期刊:
Pharmacogenetics
(OVID Available online 2000)
卷期:
Volume 10,
issue 3
页码: 261-266
ISSN:0960-314X
年代: 2000
出版商: OVID
数据来源: OVID
摘要:
Histamine is involved in the pathophysiology of asthma, and histamineN-methyltransferase (HNMT) plays the dominant role in histamine metabolism in human bronchial epithelium. Levels of HNMT activity in human tissues are controlled, in part, by inheritance. A common C314T polymorphism within the HNMT gene results in a Thr105Ilc change in encoded amino acid, and the T314 allele is associated with decreased levels of both HNMT enzymatic activity and immunoreactive protein. Therefore, presence of the T314 allele would be expected to result in reduced histamine metabolism and increased bronchoconstriction. We characterized this common, functionally significant polymorphism 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 significant increase in the frequency of subjects with low HNMT activity among asthmatics. The association between a common, functionally significant genetic polymorphism for HNMT and asthma suggests that individual variation in histamine metabolism might contribute to the pathophysiology and/or response to therapy of this disease.
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