CTLA-4 GENE POLYMORPHISM IS ASSOCIATED WITH PREDISPOSITION TO IDDM INA POPULATION FROM CENTRAL POLAND

Susceptibility to insulin-dependent diabetes mellitus (IDDM) is strong ly associated with particular HLA class II alleles. However, non-HLA g enetic factors are likely to be required for the development of the di sease. The candidate genes include the cytoxic T-lymphocyte associated -4 (CTLA-4) gene located on chromosome 2q33, which encodes a cell surf ace molecule providing a negative signal for T-cell activation. We inv estigated CTLA-4 exon 1 polymorphism (position 49 A/G) in 192 IDDM chi ldren and 136 healthy controls from Central Poland, using allele-speci fic hybridisation. The CTLA-4/G allele was found on 56.0 % of chromoso mes in IDDM patients as compared to 43.4 % in controls (p = 0.002), mo stly in homozygous form (31.2 % in patients vs 15.4 % in controls, p = 0.002). This difference was even more pronounced in non-DRB103/non-D RB104 IDDM patients (GIG genotype frequency. 35.0 % of IDDM patients vs 12.3 % of controls, p = 0.04). Our data indicate that CTLA-4 exon 1 position 49 A/G dimorphism was significantly associated with predispo sition to IDDM in our Central Poland population, particularly in patie nts lacking the strongly predisposing DRB1 alleles.