Deletion of the activating NKG2C receptor and a functional polymorphism in its ligand HLA-E in psoriasis susceptibility

Exp Dermatol. 2013 Oct;22(10):679-81. doi: 10.1111/exd.12233.

Abstract

Psoriasis is an inflammatory, immune-mediated disease of the skin. Several studies have suggested that natural killer (NK) cells and their receptors may be important for its pathogenesis. Here, we examined whether deletion of the activating natural killer receptor gene NKG2C, which has a frequency of 20% in the European population, was associated with psoriasis susceptibility. The NKG2C deletion and a functional polymorphism in its ligand HLA-E were genotyped in a Caucasian cohort of 611 psoriasis cases and 493 controls. We found that the NKG2C deletion was significantly increased in cases compared with controls [0.258 vs 0.200, P = 0.0012, OR = 1.43 (1.15-1.79)]. The low-expressing HLA-E*01:01 allele was associated with psoriasis (P = 0.0018), although this association was dependent on HLA-C. Our findings support a potential immunoregulatory role for NK cells in psoriasis and suggest the importance of future studies to investigate the contribution of NK cells and their regulatory receptors to the pathogenesis of psoriasis.

Keywords: HLA-E; KLRC2; NKG2C; natural killer; psoriasis.

Publication types

  • Letter
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Case-Control Studies
  • Cohort Studies
  • Gene Deletion
  • Genetic Predisposition to Disease*
  • Genetic Variation
  • Genotype
  • HLA-E Antigens
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Inflammation
  • Killer Cells, Natural / cytology
  • Ligands
  • NK Cell Lectin-Like Receptor Subfamily C / genetics*
  • NK Cell Lectin-Like Receptor Subfamily C / metabolism
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Psoriasis / genetics*
  • Risk Factors

Substances

  • Histocompatibility Antigens Class I
  • KLRC2 protein, human
  • Ligands
  • NK Cell Lectin-Like Receptor Subfamily C