HLA DRB1/DQA1/DQB1 haplotype determines thyroid autoimmunity in patients with insulin-dependent diabetes mellitus.

OBJECTIVE

Thyroid autoimmunity is frequently associated with insulin-dependent diabetes mellitus (IDDM). The genetic factors which contribute to thyroid autoimmunity and IDDM have been described but vary between different races. We have therefore investigated the effect of class II HLA genes at both loci and the HLA haplotypes on the presence of autoimmunity in patients with IDDM in Taiwan.

SUBJECTS AND MEASUREMENTS

Eighty-three patients with IDDM and 105 unrelated normal controls were recruited for the measurement of thyroid autoantibodies and for genotyping of HLA DRB1, DQA1 and DQB1 by polymerase chain reaction-based DNA typing techniques.

RESULTS

Among 83 patients with IDDM, 23 (27.7%) were positive for antithyroid autoantibodies. Compared to those without thyroid autoimmunity, there was a female preponderance for IDDM with thyroid autoimmunity (female: male, 3:20 vs 29:31). Among the DR specificities, DR6 was associated with a weak protective effect against thyroid autoimmunity in IDDM patients. Upon detailed analysis of class II HLA haplotypes, the DRB10301/ DQA10501/DQB10201 haplotype was found to be associated with an increased risk of IDDM regardless of thyroid autoimmunity, while DRB10405/DQA10301/ DQB10401 was significantly increased only in the IDDM patients with thyroid autoimmunity. IDDM individuals with the HLA DRB10405/DQA10301/DQB1*0302 haplotype were not at risk of thyroid autoimmunity.

CONCLUSIONS

Our data indicated that there was a generalized genetic factor within or associated with the DRB10301/DQA10501/DQB10201 haplotype, and a more restricted effect with the DRB10405/DQA10301/DQB10401 haplotype which led to thyroid autoimmunity in patients with insulin-dependent diabetes mellitus.