Can the genotype or phenotype of two polymorphic drug metabolising cytochrome P450-enzymes identify oral lichenoid drug eruptions?
BACKGROUND
Lichenoid drug eruptions (LDE) in the oral cavity are adverse drug reactions (ADR) that are impossible to differentiate from oral lichen planus (OLP) as no phenotypic criteria exist. Impaired function of polymorphic cytochrome 450-enzymes (CYPs) may cause increased plasma concentration of some drugs resulting in ADR/LDE. In an earlier study we did not find more patients with OLP (OLPs) with impaired CYP-genotype.


OBJECTIVE
To test if more OLPs have an impaired CYP-phenotype than to be expected from the CYP-genotype and to find clinical criteria characterising oral LDE.


METHODS
One hundred and twenty OLPs were genotyped for the most common polymorphisms of CYP2D6 and CYP2C19 that result in impaired function. One hundred and ten did a phenotype test of both enzymes. The exposure to drugs and polypharmacy and the CYP metabolism of the drugs were evaluated. The OLP manifestations were registered.


RESULTS
The only difference in OLP manifestations was that patients with a CYP2D6 genotype with less than two fully functional alleles presented more asymmetrical OLP distribution in particular in non-medicated patients (P < 0.05). No more OLPs than expected from the genotype had a phenotype with reduced function. However, the established phenotypic categories could not differentiate between the genotypes with two or one fully functional allele. Nevertheless, among the patients with a phenotype with normal function the patients with only one functional allele had a statistically significant higher metabolic ratio compared to patients with two fully functional alleles (P < 0.05).


CONCLUSIONS
It was not possible to identify LDE by impaired function of polymorphic CYPs.
Kragelund
C
C
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
Brosen
K
K
Jensen
S B
SB
Torpet
L A
LA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D016009:Chi-Square Distribution; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D003937:Diagnosis, Differential; D004347:Drug Interactions; D005260:Female; D005838:Genotype; D006801:Humans; D017676:Lichen Planus, Oral / Q000139:chemically induced* / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D008297:Male; D008617:Mephenytoin / Q000378:metabolism / Q000652:urine; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D019338:Polypharmacy; D013034:Sparteine / Q000378:metabolism / Q000652:urine; D018709:Statistics, Nonparametric; D011795:Surveys and Questionnaires
D013034:Sparteine; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6; D008617:Mephenytoin