ASSOCIATION OF POLYMORPHISM IN THE INTERFERON-GAMMA GENE WITH IDDM

Cytokines may play important roles in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). We analysed a dinucleotide repeat polymorphism within the first intron of the interferon gamma (IFN-gamma) gene in Japanese diabetic patients (175 IDDM and 145 non-insulin-dependent diabetes mellitus) and 267 control subjects. A significant difference was observed in the global allele distribution of the polymorphism between the IDDM and control groups (p = 0.039). The difference from the control group was more evident in the patients whose insulin therapy started within 1 year from onset (p = 0.006) or in the young-onset (< 10 years) patients (p = 0.0006). The alleles ''3'' and ''6'' were increased in the IDDM patients, and a significant increase in the frequency of the ''3/6'' genotype was observed in the IDDM patient group (9.1 %, RR 2.9, p = 0.010), in the patients with initial insulin therapy less than 1 year from onset (10.6 %, RR 3.4, p = 0.004), or in the young-onset patients (16.7 %, RR 5.7, p = 0.0003) in comparison to the control subjects (3.4 %). There was a tendency towards frequent occurrence of clinical characteristics which reflect young or abrupt onset of diabetes or both, and depletion of insulin secretion capacity in the patients with ''3/6'' or ''6/6'' in comparison to the patients with other genotypes. These results suggest that the IFN-gamma gene region may contribute to the pathogenesis of IDDM and could be a genetic marker for IDDM.