Increased frequency of HLA-Cw4 in type 2 diabetes.

In order to investigate whether there is an association between the HLA system and type 2 diabetes, we have determined HLA-A, B- and C-antigens in 227 patients with onset of diabetes between the ages of 35 and 70 years and compared them with the HLA-antigen frequencies in Finnish blood donors. One hundred and sixty-eight patients (74%) were treated with diet or oral antidiabetic drugs (non-insulin dependent), whereas 59 patients (26%) were treated with insulin (insulin-dependent). The HLA-antigen Cw4 was found in 38.7% of the non-insulin dependent patients (relative risk 2.67, p = 0.00005) and in 15.6% of the insulin dependent diabetics (relative risk 0.785 NS) compared with 19.1% in blood donors. In addition, there was an increase in the frequency of HLA-Bw35 antigen among the non-insulin dependent patients (relative risk 1.6, P = 0.007), which could be explained by the known positive linkage disequilibrium between HLA-Bw35 and HLA-Cw4. In insulin-dependent patients there was a decrease in the frequency of HLA-B7 (relative risk 0.226, P = 0.001) and an increase in the frequencies of HLA-B8 (relative risk 1.91, P = 0.031), B12 (relative risk 2.22, P = 0.01) and B15 (relative risk 2.04, P = 0.019) compared with blood donors. these data provide evidence that genes in the HLA region may have some influence in genetic susceptibility to type 2 diabetes. They further suggest that maturity onset (type 2) diabetes is a heterogeneous disease in terms of HLA antigens.(ABSTRACT TRUNCATED AT 250 WORDS)