Liver Cirrhosis Research Today is a free monthly online journal that collates and summarizes the latest research about Liver Cirrhosis, including details on alcohol, treatment, drugs, effects, causes.

Genetic polymorphisms influencing xenobiotic metabolism and transport in patients with primary biliary cirrhosis.

Kimura Y, Selmi C, Leung PS, Mao TK, Schauer J, Watnik M, Kuriyama S, Nishioka M, Ansari AA, Coppel RL, Invernizzi P, Podda M, Gershwin ME

Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, CA, USA.

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 (cl/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.

Published 4 February 2005 in Hepatology, 41(1): 55-63.
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