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Updated: Aug 14, 2026

Isolation of Fidelity Variants of RNA Viruses and Characterization of Virus Mutation Frequency
Published on: June 16, 2011
Single copy of variant CYP2A6 alleles does not confer susceptibility to liver dysfunction in patients treated with
M Burian1, J Freudenstein, M Tegtmeier
1Department of Pharmacology and Toxicology, Philipps University, Marburg, Germany. burian@em.uni-frankfurt.de
Objective:
Coumarin, used in the treatment of chronic venous diseases, is mainly metabolized to non-toxic 7-hydroxy-coumarin by CYP2A6. At least, 3 variant alleles, CYP2A6*2, CYP2A6*3 and CYP2A6*4A, have been shown to encode catalytically defective proteins. Sporadic elevation of liver enzymes has been reported on the chronic administration ofcoumarin. We sought to determine if susceptibility to coumarin-associated liver dysfunction is genetically determined by polymorphism in CYP2A6 and impairment of the 7-hydroxylation ofcoumarin. Additionally, we were interested in the effect of polymorphism on smoking because of the predominant role of CYP2A6 in the metabolism of nicotine.
Methods:
The investigation was performed prospectively within a randomized double-blind clinical trial of the coumarin-containing drug SB-LOT (90 mg coumarin + 540 mg troxerutin/d) vs. placebo in 231 German patients with chronic venous insufficiency. Monitoring of the hepatic status involved regular measurements of liver function during the 16-week treatment. Genotyping of CYP2A6 was carried out by means of PCR and confirmed by DNA sequencing analysis.
Results:
The allelic frequencies of the variant CYP2A6*2 and CYP2A6*3 alleles were 0.023 and 0.014, respectively. There was no significant difference in the incidence of liver dysfunction between heterozygotes with CYP2A6*2, CYP2A6*3 and wild-type homozygotes. CYP2A6 polymorphism had no significant effect on smoking behavior.
Conclusion:
No evidence was obtained that the studied polymorphism in CYP2A6 is a determinant of the coumarin-associated liver dysfunction.
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