1. Association of KIR2DL2 polymorphism rs2756923 with type 1 diabetes and preliminary evidence for lack of inhibition through HLA-C1 ligand binding
- Author
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F. Scholten, C. Seidl, B. Van der Auwera, Folefac Aminkeng, C. Wild, Klaus Badenhoop, Elizabeth Ramos-Lopez, H. Kalhes, T. Tonn, Diabetes Pathology & Therapy, and Medical Biochemistry
- Subjects
Cytotoxicity, Immunologic ,Male ,Genotype ,type 1 diabetes ,Immunology ,Killer-cell immunoglobulin-like receptor ,Human leukocyte antigen ,HLA-C Antigens ,Biology ,Biochemistry ,Polymorphism, Single Nucleotide ,polymorphism ,Exon ,Belgium ,Gene Frequency ,Cell Line, Tumor ,Germany ,Gene cluster ,Genetics ,medicine ,Immunology and Allergy ,Humans ,Genetic Predisposition to Disease ,Allele ,Receptor ,Alleles ,Type 1 diabetes ,Haplotype ,General Medicine ,medicine.disease ,Molecular biology ,Killer Cells, Natural ,Diabetes Mellitus, Type 1 ,Haplotypes ,Receptors, KIR2DL2 ,killer cell immunoglobulin-like receptor ,Female - 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.
- Published
- 2009