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

Lan Yan, Raymond E. Galinsky, Jonathan A. Bernstein, Stephen B. Liggett, Richard M. Weinshilboum

Research output: Contribution to journalArticle

76 Scopus citations

Abstract

Histamine is involved in the pathophysiology of asthma, and histamine N-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 Thr105Ile 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. (C) Lippincott Williams and Wilkins.

Original languageEnglish (US)
Pages (from-to)261-266
Number of pages6
JournalPharmacogenetics
Volume10
Issue number3
DOIs
StatePublished - 2000

ASJC Scopus subject areas

  • Genetics
  • Pharmacology, Toxicology and Pharmaceutics(all)

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