Polymorphic drug metabolizing CYP‐enzymes – a pathogenic factor in oral lichen planus?

Abstract

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.

Can the genotype or phenotype of two polymorphic drug metabolising cytochrome P450-enzymes identify oral lichenoid drug eruptions?

“…This is of cause interesting as unilateral manifestations have been associated with LDE (11). In an earlier study we found that more females with OLP had a poor or intermediate CYP2D6 ‐genotype when compared to control females but we could not associate impaired CYP2D6 ‐genotype to OLP unambiguously (19). However, for neither CYP2C19 or CYP2D6 were there more OLPs than expected from the genotype having a PM‐ or IM‐phenotype as 59% had a CYP2D6 ‐genotype with less than two fully functional alleles but only 25% a CYP2D6‐phenotype with reduced function.…”

“…CYP2D6*5 has a prevalence in the European population between 2–4% (44). The allele is a deletion of the CYP2D6 gene but we did not succeed getting a result using DNA extracted from bloodspots [see Kragelund et al for details (19)]. Two OLPs exposed to polypharmacy with a CYP2D6 IM/PM‐genotype had a CYP2D6 EM‐phenotype which apparently could not be explained by CYP2D6 drug‐induction.…”

“…We did find a higher prevalence of CYP2D6 IM‐ or PM‐genotypes among OLP females (59%) as compared to the control females (43%). The prevalence of CYP2D6 IM‐ or PM‐genotypes among OLP males was 59% but among the control males it was 64% (not statistically significant) (19).…”

“…The study comprised 120 Caucasian patients with OLP (OLPs) regularly monitored at the Clinic of Oral Medicine at the School of Dentistry in Copenhagen [for details see Kragelund et al (19)]. The diagnosis of OLP was established by at least two specialists on clinical manifestations of reticular and/or papular eruptions during the control period.…”

“…From all patients finger blood was obtained from which genomic DNA was extracted and CYP2D6 and CYP2C19 typed according to Kragelund et al (19). In brief, all patients were tested for the most common alleles with abolished or impaired function i.e.…”