Val/Val glutathione-S-transferase P1 polymorphism predicts nonresponders in psoriasis patients treated with fumaric acid esters

Pharmacogenet Genomics. 2016 May;26(5):248-53. doi: 10.1097/FPC.0000000000000218.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Female
  • Fumarates / therapeutic use*
  • Glutathione S-Transferase pi / genetics*
  • Humans
  • Male
  • Middle Aged
  • Pharmacogenomic Variants
  • Psoriasis / drug therapy*
  • Psoriasis / genetics*
  • Severity of Illness Index
  • Treatment Outcome
  • Valine / metabolism*

Substances

  • Fumarates
  • GSTP1 protein, human
  • Glutathione S-Transferase pi
  • Valine