ANALYSIS OF AN INTERFERON-GAMMA GENE (IFNG) POLYMORPHISM IN DANISH AND FINNISH INSULIN-DEPENDENT DIABETES-MELLITUS (IDDM) PATIENTS AND CONTROL SUBJECTS

A CA-repeat polymorphism within the first intron of the interferon (IF N)-gamma gene was analyzed. This polymorphism was recently demonstrate d to be associated with insulin-dependent diabetes mellitus (IDDM) in Japanese subjects. We typed 266 IDDM patients and 195 control subjects of Danish Caucasoid origin. No significant differences in allele or g enotype frequencies between patients and control were observed. In add ition, we typed 168 IDDM and 110 control subjects of Finnish origin. A significant disease association of the studied IFN-gamma allelic patt ern was found (p = 0.029). Analysis of data according to HLA-DQB1 susc eptibility status did not reveal heterogeneity of risk at the IFN-gamm a locus in either of the populations. Fifty-five Danish and 94 Finnish IDDM multiplex families with at least two affected siblings (660 indi viduals) were typed to test for transmission disequilibrium (TDT). No evidence for overall transmission disequilibrium using either an allel e-wise (p = 0.42; combined data) or a genotype-wise analysis (p = 0.21 ; combined data) could be detected. Thus, the modest significance leve l observed in the Finnish case-control study and the failure to replic ate it by the TDT provide little support for the hypothesis that the I FN-gamma gene microsatellite is associated with IDDM.