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

Yasuhiko Kimura, Carlo Selmi, Patrick S Leung, Tin K. Mao, Joseph Schauer, Mitchell Watnik, Shigeki Kuriyama, Mikio Nishioka, Aftab A. Ansari, Ross L. Coppel, Pietro Invernizzi, Mauro Podda, M. Eric Gershwin

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Abstract

Epidemiological data suggest that environmental factors may trigger autohnmunity 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.

Original languageEnglish (US)
Pages (from-to)55-63
Number of pages9
JournalHepatology
Volume41
Issue number1
DOIs
StatePublished - Jan 2005

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Cytochrome P-450 CYP2D6
Biliary Liver Cirrhosis
Xenobiotics
Genetic Polymorphisms
Cytochrome P-450 CYP2E1
Genotype
Multiple Drug Resistance
P-Glycoprotein
Healthy Volunteers
Alleles
Phenotype
Antigens
DNA
Genes

ASJC Scopus subject areas

  • Hepatology

Cite this

Genetic polymorphisms influencing xenobiotic metabolism and transport in patients with primary biliary cirrhosis. / Kimura, Yasuhiko; Selmi, Carlo; Leung, Patrick S; Mao, Tin K.; Schauer, Joseph; Watnik, Mitchell; Kuriyama, Shigeki; Nishioka, Mikio; Ansari, Aftab A.; Coppel, Ross L.; Invernizzi, Pietro; Podda, Mauro; Gershwin, M. Eric.

In: Hepatology, Vol. 41, No. 1, 01.2005, p. 55-63.

Research output: Contribution to journalArticle

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 2005, 'Genetic polymorphisms influencing xenobiotic metabolism and transport in patients with primary biliary cirrhosis', Hepatology, vol. 41, no. 1, pp. 55-63. https://doi.org/10.1002/hep.20516
Kimura, Yasuhiko ; Selmi, Carlo ; Leung, Patrick S ; Mao, Tin K. ; Schauer, Joseph ; Watnik, Mitchell ; Kuriyama, Shigeki ; Nishioka, Mikio ; Ansari, Aftab A. ; Coppel, Ross L. ; Invernizzi, Pietro ; Podda, Mauro ; Gershwin, M. Eric. / Genetic polymorphisms influencing xenobiotic metabolism and transport in patients with primary biliary cirrhosis. In: Hepatology. 2005 ; Vol. 41, No. 1. pp. 55-63.
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