title: Evaluation of KIR3DL1/KIR3DS1 polymorphism in Behçet's disease.
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.
authors.affiliation: Translational Genetics and Genomics Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD, USA.|Division of Rheumatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: B
authors.initials: B
authors.lastname: Erer
authors.affiliation: Inflammatory Disease Section, National Human Genome Research Institute, Bethesda, MD, USA.
authors.forename: M
authors.initials: M
authors.lastname: Takeuchi
authors.affiliation: Department of Genetics, Institute for Experimental Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: D
authors.initials: D
authors.lastname: Ustek
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: I
authors.initials: I
authors.lastname: Tugal-Tutkun
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: E
authors.initials: E
authors.lastname: Seyahi
authors.affiliation: Department of Ophthalmology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Y
authors.initials: Y
authors.lastname: Özyazgan
authors.affiliation: Department of Immunology, Institute of Health Sciences, Istanbul University, Istanbul, Turkey.
authors.forename: J
authors.initials: J
authors.lastname: Duymaz-Tozkir
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: A
authors.initials: A
authors.lastname: Gül
authors.affiliation: Inflammatory Disease Section, National Human Genome Research Institute, Bethesda, MD, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Kastner
authors.affiliation: Inflammatory Disease Section, National Human Genome Research Institute, Bethesda, MD, USA.
authors.forename: E F
authors.initials: EF
authors.lastname: Remmers
authors.affiliation: Translational Genetics and Genomics Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Ombrello
mesh_terms: D001528:Behcet Syndrome / Q000235:genetics*; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D054341:Receptors, KIR3DL1 / Q000235:genetics*; D054349:Receptors, KIR3DS1 / Q000235:genetics*
chemical_list: D006680:HLA Antigens; D054341:Receptors, KIR3DL1; D054349:Receptors, KIR3DS1