title: Significant association of the KIR2DL3/HLA-C1 genotype with susceptibility to Crohn's disease.
abstract: We aimed to analyze the possible association of KIR/HLA-C genotypes with the susceptibility to Crohn's disease (CD) in a Spanish population. A total of 125 patients with CD and 339 healthy controls were selected for this study. KIR and HLA-C typing were developed by sequence-specific oligonucleotide probing. We found that the centromeric A/A genotype and HLA-C1 combination was significantly increased in CD patients (P<10(-3)). The KIR2DL3/2DL3 genotype was significantly increased in CD patients (P<0.0005). Moreover, we also observed a highly significant increase of KIR2DL3-HLA-C1 homozygosis in CD patients (P<0.0005). Our results confirm the relevance of the KIR2DL2/KIR2DL3 genes and their interaction with HLA-C to CD. We show that the contribution of the KIR genes to CD susceptibility extends beyond the association with individual KIRs, with an imbalance between activating and inhibitory KIR genes seeming to influence the susceptibility to CD.
authors.affiliation: Department of Immunology, Hospital Universitario Central de Asturias, Oviedo, Spain; Faculty of Health Sciences, Universidad Autónoma de Chile, Talca, Chile.
authors.forename: Roberto
authors.initials: R
authors.lastname: Díaz-Peña
authors.affiliation: Department of Immunology, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Jose Ramón
authors.initials: JR
authors.lastname: Vidal-Castiñeira
authors.affiliation: Department of Immunology, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Moro-García
authors.affiliation: Department of Immunology, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Alonso-Arias
authors.affiliation: Faculty of Health Sciences, Universidad Autónoma de Chile, Talca, Chile. Electronic address: pcastros@uautonoma.cl.
authors.forename: Patricia
authors.initials: P
authors.lastname: Castro-Santos
mesh_terms: D003424:Crohn Disease / Q000235:genetics / Q000276:immunology*; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015236:HLA-C Antigens / Q000235:genetics*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D015810:Linkage Disequilibrium; D011110:Polymorphism, Genetic; D054343:Receptors, KIR2DL2 / Q000235:genetics*; D054344:Receptors, KIR2DL3 / Q000235:genetics*; D013030:Spain
chemical_list: D015236:HLA-C Antigens; C515077:KIR2DL2 protein, human; C515078:KIR2DL3 protein, human; D054343:Receptors, KIR2DL2; D054344:Receptors, KIR2DL3
keywords: Crohn’s disease; HLA; KIR; Natural killer