Background. The objective of the study was to quantify the association of insulin gene variants with type 1 diabetes mellitus (T1DM) in the Czech population. Methods and Results. In an association study, we compared genotypes of 332 T1DM patients (age at T1DM onset was 8.1±4.4 yrs) with 292 healthy nondiabetic controls of similar age. All subjects were previously genotyped for HLA-DQB1, -DQA1 polymorphisms and DRB1*04 subtypes. The insulin gene was typed using the -23 HphIsi ngle nucleotide polymorphism after we had demonstrated a nearly complete linkage disequilibrium between this polymorphism, and the etiological VNTR in the Czech population. The protective variant of the insulin gene was present in 24 % T1DMpatients, and in 48 % controls (OR=0.34, CI95% 0.24–0.48), a risk comparable to weaker-associated HLA-DQalleles. The association was independent of the HLA-conferred T1DMrisk. The insulin gene polymorphism had no influence on the age at T1DM onset. Conclusions. We conclude that the insulin gene genotyping confers important information on T1DM risk in our population, and should be used in determining the disease risk along with the HLA-DQ typing.

        Key words: insulin gene, type 1 diabetes, genetic association, children.