HLA-DQB1-ASTERISK-0602 IS ASSOCIATED WITH DOMINANT PROTECTION FROM DIABETES EVEN AMONG ISLET-CELL ANTIBODY-POSITIVE FIRST-DEGREE RELATIVES OF PATIENTS WITH IDDM

HLA-DQB1 alleles confer susceptibility and resistance to insulin-depen dent diabetes mellitus (IDDM), me investigated whether the susceptibil ity alleles DQB10302 and DQB1*0201 affect progression to diabetes amo ng islet cell antibody-positive (ICA(+)) first-degree relatives of IDD M patients and whether the protective allele DQB10602 can be found an d is still protective among such relatives, We human leukocyte antigen -typed and periodically tested beta-cell function (first-phase insulin release [FPIR] during the intravenous glucose tolerance test) in 72 I CA(+) relatives, of whom 30 became diabetic on follow-up (longest foll ow-up 12 years); 54 (75%) relatives carried DQB10302 and/or DQB1*0201 , The frequency of DQB10302 and DQB1*0201 and of the highrisk genotyp e DQB10302/DQB1*0201 did not differ significantly between diabetic re latives and those remaining nondiabetic. On follow-up, progression to IDDM was not statistically different for relatives with or without the DQB10302/DQB1*0201 genotype, However, those relatives with the DQB1* 0302/DQB10201 genotype had a tendency to develop diabetes at an earli er age (log-rank P = 0.02), We found DQB10602 in 8 of 72 (11.1%) ICA relatives, Relatives with DQB10602 did not develop diabetes or show a ny decline of FPIR versus 28 of 64 DQB10602(-) relatives who develope d IDDM (log-rank P = 0.006; Wilcoxon's P = 0.02). The protective allel e DQB10602 is found in ICA(+) relatives who have minimal risk of prog ression to IDDM. Therefore, DQB10602 is associated with protection fr om IDDM both in population studies and among relatives with evidence o f autoimmunity who should not enter prevention trials.