title: Val/Val glutathione-S-transferase P1 polymorphism predicts nonresponders in psoriasis patients treated with fumaric acid esters.
abstract: Fumaric acid esters (FAE) are beneficial in the treatment of psoriasis. However, about a third of psoriasis patients do not respond to FAE. We aimed to determine whether glutathione-S-transferase (GST) M1 and GSTP1 polymorphisms are associated with treatment outcome in psoriasis patients treated with FAE. We studied 84 psoriasis patients who were treated with FAE for 3 months. FAE nonresponders were defined as having psoriasis area and severity improvement index less than 50% after 3-month therapy. GSTM1 genotyping for gene deletion and GSTP1 exon 5 105 Ile→Val polymorphisms were assessed using a high-resolution melting analysis. A dropout rate of 23.8% (20/84) was found; 25% (16/64) were FAE nonresponders. We observed 42 (84/50%) patients with G 9STM1*0 homozygous alleles and 42 (84/50%) patients with one or two active GSTM1 alleles. The Ile/Ile GSTP1 genotype was observed in 37 (84/44%), the Ile/Val GSTP1 genotype in 38 (84/45.2%) patients and the Val/Val GSTP1 genotype in nine (84/10.7%) patients. There was no significant (P>0.05) association between the GST genotypes assessed and the frequency FAE responder status, except for the Val/Val GSTP1 polymorphism, which was a significant (overall model fit; P=0.0012) predictor for nonresponders with an odds ratio of 43.4 (95% confidence interval: 4.2-511.1). The coefficient of regression was 3.9, with a SE of 1.2 as assessed by logistic regression analysis (P=0.0017). The Val/Val GSTP1 polymorphism predicts nonresponders in FAE treatment of psoriasis patients and may therefore serve as a biomarker that enables a laboratory-based pretreatment selection of patients.
authors.affiliation: Department of Dermatology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Thilo
authors.initials: T
authors.lastname: Gambichler
authors.forename: Laura
authors.initials: L
authors.lastname: Susok
authors.forename: Julia
authors.initials: J
authors.lastname: Zankl
authors.forename: Marina
authors.initials: M
authors.lastname: Skrygan
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005650:Fumarates / Q000627:therapeutic use*; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000071184:Pharmacogenomic Variants; D011565:Psoriasis / Q000188:drug therapy* / Q000235:genetics*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014633:Valine / Q000378:metabolism*
chemical_list: D005650:Fumarates; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D014633:Valine