An exon 8 polymorphism of the KIR2DL2 gene is associated with type 1 diabetes mellitus in Germans

Killer cell immunglobulin-like receptors (KIRs) regulate the function of human natural killer-and T-cells subsets. A feature of the KIR locus on chromosome 19q13.4 is the clustering of homologous genes encoding for inhibitory and activating KIR. Given its immunological role we investigated five novel single nucleotides polymorphisms (SNPs) in the KIR2DL2 gene and one in the KIR3DS1 gene for an association with type 1 diabetes mellitus (100 controls and 100 patients). We furthermore genotyped 400 healthy controls, 400 patients suffering from type 1 diabetes mellitus and 200 families with at least one affected offspring with type 1 diabetes mellitus for the KIR-exon 8 polymorphism.

We also analysed the frequency of the KIR genes whether there is a difference between the 200 heathy controls and the 200 patients suffering from type 1 diabetes mellitus.

There was no significant association between type 1 diabetes mellitus and allelic variation of four of the KIR2DL2 polymorphisms and the KIR3DS1 polymorphism.

We found a significant association between type 1 diabetes mellitus and allelic variation of the KIR2DL2 polymorphism in exon 8 (A/G, position 13963). Our findings showed that in patients the allele “G“ had higher frequencies than in controls (p <<0,05). There was a lower transmission rate for the haplotype AG (42 transmitted vs. 92 not transmitted, p<0,0003).

There was also a significant difference between the frequency of the KIR genes. We showed that type 1 diabetes patients have less expression of the inhibitory KIRs.

We found an association between the diabetes mellitus type 1 disease and the KIR2DL2 gene. This gene could be a new marker for this disease. Further genomic investigations are underway to confirm our findings and to understand the role of the KIR genes in autoimmune diseases.