Association of Insulin Gene Variants with Type 1 Diabetes Mellitus in CzechPopulation

Overview

Background.
The objective of the study was to quantify the association of insulin gene variants with type 1 diabetesmellitus (T1DM) in the Czech population.Methods and Results. In an association study, we compared genotypes of 332 T1DM patients (age at T1DM onsetwas 8.1±4.4 yrs) with 292 healthy nondiabetic controls of similar age. All subjects were previously genotyped forHLA-DQB1, -DQA1 polymorphisms and DRB1*04 subtypes. The insulin gene was typed using the -23 HphIsi nglenucleotide 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 presentin 24 % T1DMpatients, and in 48 % controls (OR=0.34, CI95% 0.24–0.48), a risk comparable to weaker-associatedHLA-DQalleles. The association was independent of the HLA-conferred T1DMrisk. The insulin gene polymorphismhad no influence on the age at T1DM onset.Conclusions. We conclude that the insulin gene genotyping confers important information on T1DM risk in ourpopulation, 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.