title: Allelic variants of drug metabolizing enzymes as risk factors in psoriasis.
abstract: The onset or exacerbation of psoriasis, a T-cell-dependent skin disease with autoimmune features, can be triggered by drugs such as antimalarials and beta-blockers. Xenobiotics may also play a role in idiopathic psoriasis. It has been hypothesized that different metabolic efficiencies caused by variant alleles of xenobiotic metabolizing enzymes could lead to the accumulation of xenobiotics or their reactive metabolites in target organs. Subsequently, neoantigens or cryptic peptides could be presented and initiate an aggressive T cell response. In this context, we analyzed a broad array of xenobiotic metabolizing enzymes in up to 327 Caucasian psoriasis patients and compared them to 235 control persons. Alleles tested include four phase I and three phase II enzymes. Significantly more carriers of the variant alleles of CYP1A1 (alleles *2A and *2C) were found in healthy controls than in patients, suggesting a protective role for these alleles. No significant difference between patients and controls could be found, however, for the other phase I alleles 1B1*1 and 1B1 *3, 2C19*1A and 2C19*2A, and 2E1*1A and 2E1*5B. Of the variant alleles coding for phase II enzymes only GSTM1, but not GSTT1 or NQOR, correlated with a risk to contract psoriasis. Some combinations of phase I and phase II enzymes suggested protective or risk-associated effects. Interestingly, heterozygosity for CYP2C19 alleles *1A and *2A was associated with increased risk for "late onset" psoriasis, whereas this genotype was protective for psoriatic arthritis. This is the first large-scale study on these enzymes and the results obtained support the concept that different activities of metabolizing enzymes can contribute to disease etiology and progression.
authors.affiliation: Universität Düsseldorf, Hautklinik, Düsseldorf, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Richter-Hintz
authors.forename: Ricarda
authors.initials: R
authors.lastname: Their
authors.forename: Swantje
authors.initials: S
authors.lastname: Steinwachs
authors.forename: Sven
authors.initials: S
authors.lastname: Kronenberg
authors.forename: Ellen
authors.initials: E
authors.lastname: Fritsche
authors.forename: Bernd
authors.initials: B
authors.lastname: Sachs
authors.forename: Marty
authors.initials: M
authors.lastname: Wulferink
authors.forename: Torsten
authors.initials: T
authors.lastname: Tonn
authors.forename: Charlotte
authors.initials: C
authors.lastname: Esser
mesh_terms: D000328:Adult; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length; D011565:Psoriasis / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D012307:Risk Factors; D015262:Xenobiotics / Q000627:therapeutic use
chemical_list: D015262:Xenobiotics; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D019363:Cytochrome P-450 CYP1A1; D065731:Cytochrome P-450 CYP2C19