Human liver catechol-O-methyltransferase pharmacogenetics

B. Boudikova, C. Szumlanski, B. Maidak, Richard M Weinshilboum

Research output: Contribution to journalArticle

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Abstract

Catechol-O-methyltransferase activity and thermal stability in the human red blood cell are controlled by a common genetic polymorphism. Approximately 25% to 30% of a randomly selected population sample is homozygous for the traits of low catechol-O-methyltransferase activity and thermolabile enzyme in the red blood cell. We tested the hypothesis that the catechol-O-methyltransferase genetic polymorphism might also control those same characteristics of the enzyme in an important human drug-metabolizing organ, the liver. Catechol-O-methyltransferase enzyme activity and thermal stability were measured in 99 hepatic biopsy samples obtained during clinically indicated surgery. The frequency distribution of heated/control ratios, a measure of enzyme thermal stability, was bimodal, with 28% of samples included in a subgroup with thermolabile enzyme. There were no sex-related differences in hepatic catechol-O-methyltransferase thermal stability. However, catechol-O-methyltransferase enzyme activity in hepatic tissue from male subjects was significantly higher than that in samples from female subjects: 61.3 ± 20.2 units/mg protein (mean ± SD; n = 50) versus 46.6 ± 22.2 units/mg protein (n = 49; p = 0.0002). There was a significant correlation of hepatic catechol-O-methyltransferase activity and thermal stability in samples from both female (r(s) = 0.698;p = 0.0001) and male subjects (r(s) = 0.429;p = 0.002). Finally, when both red blood cell catechol-O-methyltransferase activity and thermal stability were measured in blood samples from 34 of these patients, there was a significant correlation between catechol-O-methyltransferase heated/control ratios and levels of enzyme activity in hepatic tissue and in red blood cell lysates. These findings indicate that the genetic polymorphism that controls catechol-O-methyltransferase activity level and thermal stability in red blood cells also controls those same properties of the enzyme in the human liver.

Original languageEnglish (US)
Pages (from-to)381-389
Number of pages9
JournalClinical Pharmacology and Therapeutics
Volume48
Issue number4
StatePublished - 1990

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Catechol O-Methyltransferase
Pharmacogenetics
Liver
Hot Temperature
Erythrocytes
Enzymes
Genetic Polymorphisms
Enzyme Stability
Sex Characteristics
Proteins
Biopsy

ASJC Scopus subject areas

  • Pharmacology

Cite this

Human liver catechol-O-methyltransferase pharmacogenetics. / Boudikova, B.; Szumlanski, C.; Maidak, B.; Weinshilboum, Richard M.

In: Clinical Pharmacology and Therapeutics, Vol. 48, No. 4, 1990, p. 381-389.

Research output: Contribution to journalArticle

Boudikova, B, Szumlanski, C, Maidak, B & Weinshilboum, RM 1990, 'Human liver catechol-O-methyltransferase pharmacogenetics', Clinical Pharmacology and Therapeutics, vol. 48, no. 4, pp. 381-389.
Boudikova, B. ; Szumlanski, C. ; Maidak, B. ; Weinshilboum, Richard M. / Human liver catechol-O-methyltransferase pharmacogenetics. In: Clinical Pharmacology and Therapeutics. 1990 ; Vol. 48, No. 4. pp. 381-389.
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