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

Authors

  • Xue Zeng,

    1. Department of Dermatology, University of California San Francisco, San Francisco, CA, USA
    2. Department of Dermatology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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  • Haoyan Chen,

    1. Department of Dermatology, University of California San Francisco, San Francisco, CA, USA
    2. Department of Gastroenterology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Digestive Diseases, Shanghai, China
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  • Rashmi Gupta,

    1. Department of Dermatology, University of California San Francisco, San Francisco, CA, USA
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  • Oscar Paz-Altschul,

    1. Department of Dermatology, University of California San Francisco, San Francisco, CA, USA
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  • Anne M. Bowcock,

    1. Cancer Genomics and National Heart and Lung Institute, Imperial College, London, UK
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  • Wilson Liao

    Corresponding author
    • Department of Dermatology, University of California San Francisco, San Francisco, CA, USA
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Correspondence: Wilson Liao, Department of Dermatology, University of California San Francisco, San Francisco, CA, USA, Tel.: 415-476-8364, Fax: 415-476-8837, e-mail: LiaoWi@derm.ucsf.edu

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 (= 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.

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