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Evaluation of KIR3DL1/KIR3DS1 polymorphism in Behçet’s disease

Genes & Immunity volume 17, pages 396–399 (2016)Cite this article

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Abstract

The Behçet’s disease (BD)-associated human leukocyte antigen (HLA) allele, HLA-B*51 (B*51), encodes a ligand for a pair of allelic killer immunoglobulin-like receptors (KIR) present on cytotoxic cells—KIR3DL1, which inhibits their cytotoxicity, and KIR3DS1, which activates their cytotoxic activity. We tested whether KIR-regulated mechanisms contribute to BD by testing for association of KIR3DL1/KIR3DS1 genotypes with disease in 1799 BD patients and 1710 healthy controls from Turkey, as well as in different subsets of individuals with HLA-type-defined ligands for the KIR3D receptors. HLA types were imputed from single nucleotide polymorphism genotypes determined with the Immunochip. The presence of inhibitory KIR3DL1 or activating KIR3DS1 alleles did not differ significantly between cases and controls (KIR3DL1: 92.9% vs 93.4%, Pdominant=0.55; KIR3DS1: 42.7% vs 41.0%, Pdominant=0.29). The KIR3DL1/KIR3DS1 alleles were also present at similar frequencies among cases and controls bearing HLA-B with a Bw4 motif; HLA-B with a Bw4 motif with isoleucine at position 80; and HLA-B*51. Our results suggest that pathogenic mechanisms associated with HLA-B*51 do not primarily involve differential interactions with KIR3DL1 and KIR3DS1 receptors. However, due to the complexity of this locus (that is, sequence variation and copy number variation), we cannot exclude a role for other types of KIR variation in the pathogenesis of BD.

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Acknowledgements

This work was supported by the Intramural Research Programs of the National Institute of Arthritis and Muscuoskeletal and Skin Diseases (Z01-AR041198) and the National Human Genome Research Institute (Z01-HG200370) of the National Institutes of Health.

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Authors and Affiliations

  1. Translational Genetics and Genomics Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD, USA

    B Erer & M J Ombrello

  2. Division of Rheumatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey

    B Erer, I Tugal-Tutkun & A Gül

  3. Inflammatory Disease Section, National Human Genome Research Institute, Bethesda, MD, USA

    M Takeuchi, D L Kastner & E F Remmers

  4. Department of Genetics, Institute for Experimental Medicine, Istanbul University, Istanbul, Turkey

    D Ustek

  5. Division of Rheumatology, Department of Internal Medicine, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey

    E Seyahi

  6. Department of Ophthalmology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey

    Y Özyazgan

  7. Department of Immunology, Institute of Health Sciences, Istanbul University, Istanbul, Turkey

    J Duymaz-Tozkir

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  1. B Erer
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Correspondence to B Erer.

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Erer, B., Takeuchi, M., Ustek, D. et al. Evaluation of KIR3DL1/KIR3DS1 polymorphism in Behçet’s disease. Genes Immun 17, 396–399 (2016). https://doi.org/10.1038/gene.2016.36

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  • DOI: https://doi.org/10.1038/gene.2016.36

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