ASSOCIATION OF INTERCELLULAR ADHESION MOLECULE-1 469 E/K POLYMORPHISM WITH TYPE 1 DIABETES

Abstract

Type 1 diabetes is a disease with autoimmune pathogenesis, mainly conditioned by genetic susceptibility factors. Recent studies (mainly on NOD mice) showed the importance of Intercellular Adhesion Molecule-1 (ICAM-1) in the autoimmune destruction of pancreatic  cells. We checked the possible association of ICAM-1 with type 1 diabetes genetic susceptibility on 204 Romanian diabetic simplex families, country with one of the lowest incidences of type 1 diabetes in Europe. For this we used the Sequence Specific Primer-Polymerase Chain Reaction (PCR-SSP) technique to type 469 E/K and 2412 G/R alleles of ICAM-1 gene on chromosome 19p13.3-2. The data were analysed using the Transmission Disequilibrium Test (TDT).
We found for the Romanian population a significant increased transmission of 469 E allele to diabetics (63.54%, p=0.00011). We tried to replicate the data on 243 Sardinian and 424 UK families. We could confirm the association of 469 E allele with type 1 diabetes susceptibility for the Sardinian families (p=0.013) but not for the UK families (p=0.87). However, for these populations we found a trend of increased transmission of 469 E allele from mothers to diabetic offspring. The combined analysis of x families showed a significant increased maternal transmission (59.42%, p=0.0007). We did not observe differences in transmission for offspring stratified according to age at onset.
In conclusion we found an association of ICAM-1 469E allele with type 1 diabetes risk for the Latin Romanian and Sardinian populations but not for the UK population.