Background: The objective of the study was to quantify the association of insulin gene variants with type 1 diabetes mellitus (TIDM) 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 HphI single 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% T1DM patients, and in 48% controls (OR=0.34, CI 95% 0.24-0.48), a risk comparable to weaker-associated HLA-DQ alleles. The association was independent of the HLA-conferred T1DM risk. 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.