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-dependent diabetes mellitus (IDDM), me investigated whether the susceptibility alleles DQB1*0302 and DQB1*0201 affect progression to diabetes among islet cell antibody-positive (ICA(+)) first-degree relatives of IDDM patients and whether the protective allele DQB1*0602 can be found and 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 ICA(+) relatives, of whom 30 became diabetic on follow-up (longest follow-up 12 years); 54 (75%) relatives carried DQB1*0302 and/or DQB1*0201, The frequency of DQB1*0302 and DQB1*0201 and of the highrisk genotype DQB1*0302/DQB1*0201 did not differ significantly between diabetic relatives and those remaining nondiabetic. On follow-up, progression to IDDM was not statistically different for relatives with or without the DQB1*0302/DQB1*0201 genotype, However, those relatives with the DQB1*0302/DQB1*0201 genotype had a tendency to develop diabetes at an earlier age (log-rank P = 0.02), We found DQB1*0602 in 8 of 72 (11.1%) ICA relatives, Relatives with DQB1*0602 did not develop diabetes or show any decline of FPIR versus 28 of 64 DQB1*0602(-) relatives who developed IDDM (log-rank P = 0.006; Wilcoxon's P = 0.02). The protective allele DQB1*0602 is found in ICA(+) relatives who have minimal risk of progression to IDDM. Therefore, DQB1*0602 is associated with protection from IDDM both in population studies and among relatives with evidence of autoimmunity who should not enter prevention trials.