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Vol. 30, Issue 2, 129-134, February 2002
Departments of Gastroenterology (M.C., M.L.M., P.V.D.) and
Pathology (J.L.S.), and the University of Melbourne Department of
Medicine (M.C., P.V.D.), St. Vincent's Hospital, Melbourne, Australia
The UDP glucuronosyltransferases (UGT) are a family of
enzymes in which substrates include drugs, xenobiotics, and products of
endogenous catabolism. The main source of most UGT enzymes is the
liver, a major organ in the detoxification and inactivation of
compounds. Previous studies have indicated that glucuronidation, as
measured by pharmacokinetic studies, is relatively spared in liver
disease. Because UGT activity toward most substrates is the result of
metabolism by different isoforms with overlapping specificities, these
studies may not indicate the effect of disease on the levels of
individual isoforms. We sought to extend these studies to the
measurement of mRNA for individual isoforms in the liver of patients
with various forms of liver disease. RNA was extracted from liver
tissue samples of patients undergoing clinically necessary percutaneous
liver biopsies. UGT mRNA levels for isoforms 1A1, 1A3, 1A4, 1A6, 1A9,
2B4, 2B7, 2B10, 2B11, 2B15, and 2B17 were determined by real-time
reverse transcription-polymerase chain reaction. Biopsies were
graded using the Metavir system. Results from patients with low
fibrosis or inflammatory scores were compared with those with high
scores. We found large interindividual variation in the levels of the
various isoforms. This was greatest for UGT2B17. A consistent downward
trend, reaching statistical significance for UGT1A4, UGT2B4, and
UGT2B7, was observed in samples from patients with high inflammation
scores. There was no such correlation with the degree of fibrosis. Our
results indicate that hepatic UGT mRNA levels are reduced while the
tissue is inflamed, but they are not affected in the noninflamed,
chronically diseased liver.
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