Linkage disequilibrium testing of four interleukin-1 gene-cluster polymorphisms in Danish multiplex families with insulin-dependent diabetes mellitus

The molecules of the interleukin 1 (IL-1) system have been suggested to play a role in the pathogenesis of insulin-dependent diabetes mellitus (IDDM), and polymorphisms in the genes encoding IL-1beta (IL1B), the IL-1 Type 1 receptor (IL1RTI) and the IL-1 receptor antagonist (IL1RN) molecules have been associated with IDDM in case-control studies. It can be difficult to exclude selection biases in case-control studies leading to spurious association. This risk is eliminated when using the transmission disequilibrium test (TDT). Hence, by means of the TDT we have investigated four intragenic IL-1 gene-cluster polymorphisms, the IL1B AvaI, the IL1B TaqI, the IL1RTI PstI and the IL1RN 2(nd)intron polymorphisms, for linkage and intra-familial association with IDDM in Danish IDDM multiplex family material comprising 245 families. We found no evidence for overall linkage or intra-familial association between any of the polymorphisms and IDDM. In addition, we did not find linkage between any of the polymorphisms and IDDM in HLA-DR3/4 heterozygous or HLA-non-DR3/4 heterozygous IDDM subjects, respectively. In conclusion, by means of intra-familial TDT analysis we found no linkage or intra-familial association between IDDM and the four IL-1 gene-cluster polymorphisms in Danish IDDM multiplex family material.