Subgrouping of patients with oral lichen planus according to cytochrome P450 enzyme phenotype and genotype.

OBJECTIVE: This study aimed to determine if the activity of the environmentally influenced cytochrome P450 enzyme CYP1A2, alone or in combination with CYP2D6*4 genotype, discriminates subgroups of oral lichen planus (OLP) according to lifestyle factors and clinical manifestations. STUDY DESIGN: A total of 111 patients with OLP were categorized according to normal, low, or high CYP1A2 activity and CYP2D6 4 genotype. Lifestyle parameters influencing the CYP1A2 activity and symptoms and manifestations of OLP were recorded. RESULTS: Of the 111 patients, 21% had low, 65% normal, and 14% high CYP1A2 activity. The high-CYP1A2-activity group was more exposed to CYP1A2 inducers than the low-CYP1A2-activity group. In the normal-CYP1A2-activity group, more patients had a CYP2D6 4 genotype (58%) (P = .02), and they presented more symptoms (P = .003) and gingival lesions (P = .03). More patients in the low-CYP1A2-activity group and without CYP2D6 4 genotype presented red lesions (P = .04). CONCLUSIONS: We suggest CYP2D6 4 genotype as a disease-susceptible genotype and low or high CYP1A2 activity levels as indicators of environmental influence in OLP subgroups.

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. 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.