HLA-DQB1-ASSOCIATED SUSCEPTIBILITY THAT DISTINGUISHES HASHIMOTOS-THYROIDITIS FROM GRAVES-DISEASE IN TYPE-I DIABETIC-PATIENTS

Insulin-dependent diabetes (IDDM) is frequently associated with autoim mune thyroid disease (ATD) within families. In these families, HLA pol ymorphism may modulate the susceptibility to each disease. Families wi th IDDM were further categorized as to the presence of ATD. IDDM-affec ted subjects from families without ATD were compared with subjects wit h ATD or with IDDM and ATD from IDDM/ ATD families and with a control group. IDDM susceptibility in IDDM/ ATD families was negatively associ ated with the presence of DQB10602 [relative risk (RR) = 0.038; P = 0 .0001; corrected P (Pc) = 0.0005] and 0301 (RR = 0.3; P = 0.002; Pc = 0.01) and positively associated with the presence of DQB10201 (RR = 3.4; P = 0.0007; Pc = 0.0035) and 0302 (RR = 5; P = 0.0001; Pc = 0.00 05), regardless of ATD. Compared with the IDDM-only group, the ATD-onl y group had an increased frequency of subjects with DQB10602 (RR = 0. 14; P = 0.031), suggesting that the known IDDM-protective effect of th is allele may be independent of susceptibility to ATD; however, this d ifference was not significant when the P value was corrected for the n umber of alleles tested. In these families, susceptibility to ATD was only associated with DQB10201 (RR = 5.71; P = 0.0043; Pc = 0.021). Am ong subjects with DQB10201, there was a weak negative association bet ween the presence of DQB10302 on the second haplotype and Hashimoto's thyroiditis (RR = 0.237; P = 0.026; Pc > 0.05). We conclude that in I DDM/ATD families, IDDM-affected subjects are at risk for ATD, especial ly those carrying DQB10201. This risk may be influenced by the allele s carried on the second haplotype, with DQB10302 (or a closely linked gene) protecting from Hashimoto's thyroiditis and favoring Graves' di sease.