Polymorphic drug metabolizing CYP-enzymes--a pathogenic factor in oral lichen planus?
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.


OBJECTIVE
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.


CONCLUSIONS
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.
Kragelund
C
C
Section of Oral Medicine, Clinical Oral Physiology, Oral Pathology & Anatomy, Department of Odontology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. ckr@odont.ku.dk
Hansen
C
C
Reibel
J
J
Nauntofte
B
B
Broesen
K
K
Pedersen
A M L
AM
Smidt
D
D
Eiberg
H
H
Torpet
L A
LA
D000328:Adult; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D016022:Case-Control Studies; D015331:Cohort Studies; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D019587:Dietary Supplements; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D017676:Lichen Planus, Oral / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D018716:Molecular Mimicry / Q000235:genetics; D004366:Nonprescription Drugs / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010946:Plants, Medicinal / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies
D004366:Nonprescription Drugs; D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6