HLA-G 14-bp polymorphism: a possible marker of systemic treatment response in psoriasis vulgaris? Preliminary results of a retrospective study

Dermatol Ther. 2014 Sep-Oct;27(5):284-9. doi: 10.1111/dth.12140. Epub 2014 Jun 9.

Abstract

Human leukocyte antigen-G (HLA-G) is a nonclassical HLA class I molecule that exerts an immunosuppressive function. A 14-base pair (bp) sequence insertion/deletion (INS/DEL) polymorphism in the exon 8 at the 3' untranslated region (UTR) modifies mRNA stability and protein production and has been shown to concur with efficacy of pharmacological treatments in immune-mediated conditions. The aim of this study was to assess for the first time the correlation between HLA-G 14-bp INS/DEL polymorphism with the response to systemic therapy in psoriatic patients. We retrospectively analyzed the HLA-G 14-bp INS/DEL polymorphism of HLA-G gene in patients with moderate to severe plaque psoriasis: 21 treated with acitretin, 16 with cyclosporine, 11 with anti-TNF-α. Patients who reached PASI 75 at weeks 10-16 were considered responders. Among patients treated with acitretin, we observed a significantly increased frequency of the HLA-G DEL allele and of the DEL/DEL genotype in responder patients when compared with nonresponders. An association between HLA-G genotype and response to cyclosporine and biologics was not found. The significant association between HLA-G 14-bp DEL allele and 14-bp DEL/DEL genotype and acitretin clinical outcome may suggest an advantage of this allele and propose this HLA-G polymorphism as a potential marker of response to acitretin in psoriatic patients.

Keywords: 14-bp polymorphism; HLA-G; immune-modulation; pharmacogenetics; psoriasis; systemic therapy.

MeSH terms

  • 3' Untranslated Regions
  • Acitretin / therapeutic use*
  • Adult
  • Aged
  • Aged, 80 and over
  • Base Pairing
  • Biological Products / therapeutic use
  • Cyclosporine / therapeutic use
  • Dermatologic Agents / therapeutic use*
  • Exons
  • Gene Frequency
  • Genotype
  • HLA-G Antigens / genetics*
  • Humans
  • Male
  • Middle Aged
  • Pharmacogenetics
  • Phenotype
  • Polymorphism, Genetic*
  • Psoriasis / diagnosis
  • Psoriasis / drug therapy*
  • Psoriasis / genetics*
  • Psoriasis / immunology
  • Retrospective Studies
  • Severity of Illness Index
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

  • 3' Untranslated Regions
  • Biological Products
  • Dermatologic Agents
  • HLA-G Antigens
  • Tumor Necrosis Factor-alpha
  • Cyclosporine
  • Acitretin