Deletion of the activating NKG2C receptor and a functional polymorphism in its ligand HLA-E in psoriasis susceptibility.
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.
Department of Dermatology, University of California San Francisco, San Francisco, CA, USA; Department of Dermatology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Xue
X
Zeng
Haoyan
H
Chen
Rashmi
R
Gupta
Oscar
O
Paz-Altschul
Anne M
AM
Bowcock
Wilson
W
Liao
D000483:Alleles; D016022:Case-Control Studies; D015331:Cohort Studies; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D007694:Killer Cells, Natural / Q000166:cytology; D008024:Ligands; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011565:Psoriasis / Q000235:genetics*; D012307:Risk Factors; D000097625:HLA-E Antigens
D015395:Histocompatibility Antigens Class I; D008024:Ligands; D055654:NK Cell Lectin-Like Receptor Subfamily C; D000097625:HLA-E Antigens; C527059:KLRC2 protein, human
HLA-E; KLRC2; NKG2C; natural killer; psoriasis