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

Bidragets oversatte titel: Kan genotypen eller fænotypen med hensyn til to polymorfe lægemiddelmetaboliserende cytokrom P450 enzymer identificere orale lichenoid eruptioner?

C Kragelund, C Hansen, J Reibel, B Nauntofte, K Brosen, S B Jensen, L A Torpet

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.

OBJECTIVES: 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).

CONCLUSION: It was not possible to identify LDE by impaired function of polymorphic CYPs.

OriginalsprogEngelsk
TidsskriftJournal of Oral Pathology & Medicine
Vol/bind39
Udgave nummer6
Sider (fra-til)497-505
ISSN0904-2512
DOI
StatusUdgivet - jul. 2010

Fingeraftryk

Lichenoid Eruptions
Drug Eruptions
Oral Lichen Planus
Cytochrome P-450 Enzyme System
Alleles
Pharmaceutical Preparations
Cytochrome P-450 CYP2D6
Drug-Related Side Effects and Adverse Reactions
Enzymes
Cytochromes

Emneord

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Aryl Hydrocarbon Hydroxylases
  • Chi-Square Distribution
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 CYP2D6
  • Diagnosis, Differential
  • Drug Interactions
  • Female
  • Genotype
  • Humans
  • Lichen Planus, Oral
  • Male
  • Mephenytoin
  • Middle Aged
  • Phenotype
  • Polymorphism, Genetic
  • Polypharmacy
  • Questionnaires
  • Sparteine
  • Statistics, Nonparametric

Citer dette

Kragelund, C ; Hansen, C ; Reibel, J ; Nauntofte, B ; Brosen, K ; Jensen, S B ; Torpet, L A. / Can the genotype or phenotype of two polymorphic drug metabolising cytochrome P450-enzymes identify oral lichenoid drug eruptions?. I: Journal of Oral Pathology & Medicine. 2010 ; Bind 39, Nr. 6. s. 497-505.
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title = "Can the genotype or phenotype of two polymorphic drug metabolising cytochrome P450-enzymes identify oral lichenoid drug eruptions?",
abstract = "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.OBJECTIVES: 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).CONCLUSION: It was not possible to identify LDE by impaired function of polymorphic CYPs.",
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Can the genotype or phenotype of two polymorphic drug metabolising cytochrome P450-enzymes identify oral lichenoid drug eruptions? / Kragelund, C; Hansen, C; Reibel, J; Nauntofte, B; Brosen, K; Jensen, S B; Torpet, L A.

I: Journal of Oral Pathology & Medicine, Bind 39, Nr. 6, 07.2010, s. 497-505.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Can the genotype or phenotype of two polymorphic drug metabolising cytochrome P450-enzymes identify oral lichenoid drug eruptions?

AU - Kragelund, C

AU - Hansen, C

AU - Reibel, J

AU - Nauntofte, B

AU - Brosen, K

AU - Jensen, S B

AU - Torpet, L A

PY - 2010/7

Y1 - 2010/7

N2 - 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.OBJECTIVES: 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).CONCLUSION: It was not possible to identify LDE by impaired function of polymorphic CYPs.

AB - 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.OBJECTIVES: 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).CONCLUSION: It was not possible to identify LDE by impaired function of polymorphic CYPs.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Alleles

KW - Aryl Hydrocarbon Hydroxylases

KW - Chi-Square Distribution

KW - Cytochrome P-450 CYP2C19

KW - Cytochrome P-450 CYP2D6

KW - Diagnosis, Differential

KW - Drug Interactions

KW - Female

KW - Genotype

KW - Humans

KW - Lichen Planus, Oral

KW - Male

KW - Mephenytoin

KW - Middle Aged

KW - Phenotype

KW - Polymorphism, Genetic

KW - Polypharmacy

KW - Questionnaires

KW - Sparteine

KW - Statistics, Nonparametric

U2 - 10.1111/j.1600-0714.2010.00897.x

DO - 10.1111/j.1600-0714.2010.00897.x

M3 - Journal article

C2 - 20492431

VL - 39

SP - 497

EP - 505

JO - Journal of Oral Pathology & Medicine

JF - Journal of Oral Pathology & Medicine

SN - 0904-2512

IS - 6

ER -