Variable expression of CYP and Pgp genes in the human small intestine

Lindell, M., Karlsson, M. O., Lennernas, H., Pahlman, L and Lang, M. A. (2003) Variable expression of CYP and Pgp genes in the human small intestine. European Journal of Clinical Investigation, 33 6: 493-499. doi:10.1046/j.1365-2362.2003.01154.x

Author Lindell, M.
Karlsson, M. O.
Lennernas, H.
Pahlman, L
Lang, M. A.
Title Variable expression of CYP and Pgp genes in the human small intestine
Journal name European Journal of Clinical Investigation   Check publisher's open access policy
ISSN 0014-2972
Publication date 2003-06
Sub-type Article (original research)
DOI 10.1046/j.1365-2362.2003.01154.x
Volume 33
Issue 6
Start page 493
End page 499
Total pages 7
Place of publication Oxford, OX4, United Kingdom
Publisher Wiley-Blackwell
Language eng
Formatted abstract
Background: The small intestine is receiving increased attention for its importance in drug metabolism. However, knowledge of the intervariability and regulation of the enzymes involved, cytochrome P450 and P-Glycoproteins (CYP and Pgp), is poor when compared with the corresponding hepatic enzymes.

Methods: The expression of eight different CYP genes and the Pgp were determined by reverse transcription polymerase chain reaction (RT-PCR) in 51 human duodenum biopsies. And the variability and correlation of expression was analyzed.

Results: Extensive interindividual variability was found in the expression of most of the genes. Only CYP2C9, CYP3A4 and Pgp were found in all samples. CYP1A2, CYP2A6 and CYP2E1 exhibited the highest interindividual variability. No strong correlation of expression existed between the genes. But a highly significant correlation was found between CYP2D6/1A2, 2D6/2E1, 1A2/2E1 and 2B6/2C9. Acetylsalicylic acid and omeprazole significantly increased the expression of CYPs 2A6, 2E1 and 3A4, respectively.

Conclusions: Extensive interindividual variability is characteristic for the expression of drug-metabolizing CYP and Pgp genes in human duodenum, and external factors such as drugs may further increase the variability. It is possible that the large inter-individual variability may lead to variable bioavailability of orally used drugs and hence complicate optimal drug therapy, especially for drugs with a small therapeutic window. Elucidation of factors contributing to clinically important variances warrants further investigation.
Keyword Cytochrome P450
mRNA expression
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: National Research Centre for Environmental Toxicology Publications
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Created: Wed, 09 Feb 2011, 10:48:30 EST