Premium
Genetic polymorphisms influencing xenobiotic metabolism and transport in patients with primary biliary cirrhosis
Author(s) -
Kimura Yasuhiko,
Selmi Carlo,
Leung Patrick S. C.,
Mao Tin K.,
Schauer Joseph,
Watnik Mitchell,
Kuriyama Shigeki,
Nishioka Mikio,
Ansari Aftab A.,
Coppel Ross L.,
Invernizzi Pietro,
Podda Mauro,
Gershwin M. Eric
Publication year - 2005
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.20516
Subject(s) - primary biliary cirrhosis , xenobiotic , drug metabolism , metabolism , medicine , primary (astronomy) , gastroenterology , biology , biochemistry , enzyme , physics , astronomy
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. (H EPATOLOGY 2005;41:55–63.)