title: Association of KIR2DL2 polymorphism rs2756923 with type 1 diabetes and preliminary evidence for lack of inhibition through HLA-C1 ligand binding.
abstract: Killer cell immunoglobulin-like receptors (KIRs) on chromosome 19q13.4 regulate the function of not only human natural killer (NK) cells but also T cells. An increase in activating KIR- human leucocyte antigen ligand pairs has been associated with an additional risk to develop type 1 diabetes (T1D). T1D families [n = 184 (552 individuals); n = 176 (528 subjects)], unrelated T1D patients (n = 380; n = 394) and healthy controls (n = 315; n = 401) from Germany and Belgium, respectively, were genotyped for the rs2756923 polymorphism within the KIR gene cluster haplotype B in exon 8 of the KIR2DL2 gene. We observed in both Germans and Belgians an overtransmission of the allele 'G' of the KIR2DL2-rs2756923 polymorphism (64.2% vs 35.8%, P = 3 x 10(-4) and 60.0% vs 40.0%, P = 0.02, respectively). In addition, this allele was more frequent in German patients than in healthy controls (78.4% vs 21.6%, P = 1 x 10(-3)). Preliminary results from a cytotoxicity assay suggest that inhibition of NK-cell cytotoxicity may be impaired in individuals carrying the rs2756923 G allele. These data suggest a potential role of the KIR2DL2-rs2756923 polymorphism in T1D in Germans and Belgians.
authors.affiliation: Department of Internal Medicine I, Division of Endocrinology, Diabetes and Metabolism, University Hospital Frankfurt, Frankfurt am Main, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Ramos-Lopez
authors.forename: F
authors.initials: F
authors.lastname: Scholten
authors.forename: F
authors.initials: F
authors.lastname: Aminkeng
authors.forename: C
authors.initials: C
authors.lastname: Wild
authors.forename: H
authors.initials: H
authors.lastname: Kalhes
authors.forename: C
authors.initials: C
authors.lastname: Seidl
authors.forename: T
authors.initials: T
authors.lastname: Tonn
authors.forename: B
authors.initials: B
authors.lastname: Van der Auwera
authors.forename: K
authors.initials: K
authors.lastname: Badenhoop
mesh_terms: D000483:Alleles; D001530:Belgium; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000235:genetics / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany; D015236:HLA-C Antigens / Q000235:genetics* / Q000378:metabolism; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D054343:Receptors, KIR2DL2 / Q000235:genetics* / Q000276:immunology
chemical_list: D015236:HLA-C Antigens; D054343:Receptors, KIR2DL2