Premium
Polymorphic drug metabolizing CYP‐enzymes – a pathogenic factor in oral lichen planus?
Author(s) -
Kragelund C.,
Hansen C.,
Reibel J.,
Nauntofte B.,
Broesen K.,
Pedersen A. M. L.,
Smidt D.,
Eiberg H.,
Torpet L. A.
Publication year - 2009
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/j.1600-0714.2008.00702.x
Subject(s) - pathogenesis , cyp2d6 , biology , genotype , cytochrome p450 , candida albicans , population , oral lichen planus , cyp2c19 , allele , cyp2c9 , drug metabolism , immunology , genetics , drug , medicine , gene , pharmacology , endocrinology , metabolism , environmental health
Background: Oral lichen planus (OLP) is a chronic mucosal disease with a characteristic clinical phenotype. Environmental exposures, e.g. drugs have been associated with the pathogenesis. Objectives: To test the hypothesis that some OLP lesions have a pharmacological pathogenesis related to polymorphisms of the cytochrome P450 enzymes (CYPs) resulting in poor or intermediate CYP metabolism. Methods: One hundred and twenty patients with OLP and 180 gender‐matched controls without OLP were genotyped for CYP2C9 , CYP2C19 , and CYP2D6 alleles with absent or reduced function. Results: The prevalence of poor or intermediate metabolizers was not higher among the OLPs as compared with the controls; however, there were higher numbers of variant CYP2D6 genotypes among the OLP females ( P < 0.05). There were no differences between the groups with regard to intake of drugs metabolized by polymorphic CYPs or drug or herbal products inhibiting CYPs. The prevalence of CYP2D6*4 alleles among the OLPs was higher [28%; 95% confidence interval (CI) 20–36%] than previously reported among Danes (19%; 95% CI 17–22%). Fifty per cent of the OLPs had a CYP2D6*4 genotype as compared with 30% in the background population ( P = 0.0001). The CYP2D6*4 protein has sequence homology with human herpes simplex virus type 1 (HSV1) and Candida albicans , which may result in molecular mimicry. Conclusion: It was not possible to substantiate a pharmacological pathogenesis of OLP based on poor or intermediate CYP metabolism. However, molecular mimicry between CYP2D6, in particular CYP2D6*4, and common oral pathogens may be involved in the pathogenesis of OLP.