Killer cell immunoglobulin-like receptor along with HLA-C ligand genes are associated with type 1 diabetes in Chinese Han population

Objective: Killer cell immunoglobulin-like receptor (KIR) genes and their putative ligands human leukocyte antigen (HLA)-C genes have been associated with type 1 diabetes (T1D). We hypothesize that KIR genes and their ligands HLA-C genes are important in T1D aetiology.

Research design and methods: KIR and HLA-C ligand genotyping was performed in 259 T1D patients and 262 healthy children.

Results: No significant difference was observed in the distribution of KIR genes between T1D patients and healthy controls. However, frequency of HLA-C1 gene and HLA-C2 gene (marginal association) was higher in patient group. The combinations 2DL2-/HLA-C1+; 2DL3+/HLA-C1+; 2DS2-/HLAC1+ were positively associated with T1D. The combinations 2DL1+/HLA-C2-; 2DL2-/HLA-C1-; 2DL3+/HLA-C1-; 2DS2-/HLAC1- were found to be negatively associated with T1D. Among the genes we tested, a combination of HLA-C1 and -C2 conferred the strongest association with T1D and the strength of this association was higher than that of HLA-C1 alone. The frequencies of KIR 2DL1, 2DL2 and 2DL3 and HLA-C1 were higher in T1D patients positive for GAD65 autoantibody; frequency of KIR 2DS4 is higher in T1D patients positive for IA-2 autoantibody. The association between KIR/HLA-C gene and autoantibody status was not statistically significant after applying Bonferroni correction.

Conclusion: In our study of a Han population (East China), we found no direct association of KIR genes with T1D. However, a combination of HLA-C1 and -C2 showed a positive association with T1D. Different combinations of HLA-C and KIR showed positive and negative association with T1D.