Y.K. and C.S. contributed equally to the study.
Liver Failure and Liver Disease
Genetic polymorphisms influencing xenobiotic metabolism and transport in patients with primary biliary cirrhosis†
Article first published online: 22 DEC 2004
Copyright © 2004 American Association for the Study of Liver Diseases
Volume 41, Issue 1, pages 55–63, January 2005
How to Cite
Kimura, Y., Selmi, C., Leung, P. S. C., Mao, T. K., Schauer, J., Watnik, M., Kuriyama, S., Nishioka, M., Ansari, A. A., Coppel, R. L., Invernizzi, P., Podda, M. and Gershwin, M. E. (2005), Genetic polymorphisms influencing xenobiotic metabolism and transport in patients with primary biliary cirrhosis. Hepatology, 41: 55–63. doi: 10.1002/hep.20516
Conflict of interest: Nothing to report.
- Issue published online: 23 DEC 2004
- Article first published online: 22 DEC 2004
- Manuscript Accepted: 13 OCT 2004
- Manuscript Received: 24 APR 2004
- National Institutes of Health. Grant Number: 39588
Epidemiological data suggest that environmental factors may trigger autoimmunity in genetically susceptible individuals. In primary biliary cirrhosis (PBC), it has been postulated that halogenated xenobiotics can modify self-molecules, facilitating the breakdown of tolerance to mitochondrial antigens. The transport and metabolism of xenobiotics is highly dependent on key genetic polymorphisms that alter enzymatic phenotype. We analyzed genomic DNA from 169 patients with PBC and 225 geographically and sex-matched healthy subjects for polymorphisms of genes coding for cytochromes P450 (CYPs) 2D6 (CYP2D6*4, CYP2D6*3, CYP2D6*5, and CYP2D6*6) and 2E1 (c1/c2), multidrug resistance 1 (MDR1 C3435T) P-glycoprotein, and pregnane X receptor (PXR C-25385T, C8055T, and A7635G). We compared the genotype frequencies in patients and controls and also correlated polymorphisms with PBC severity. The distributions of the studied genotypes did not significantly differ between patients and controls. However, when clinical characteristics of patients with PBC were compared according to genotype, the CYP2E1 c2 allele was associated with signs of more severe disease. In conclusion, genetic polymorphisms of CYP 2D6 and 2E1, PXR, and MDR1 do not appear to play a role in the onset of PBC. (HEPATOLOGY 2005;41:55–63.)