Polymorphisms of HLA class II predispose children and adolescents with type 1 diabetes mellitus to autoimmune thyroid disease

To determine the prevalence of autoimmune thyroid disease (AITD) in children and adolescents with type 1 diabetes mellitus (DM), and assess whether the development of AITD is correlated with specific DQ-A and DQ-B loci of the HLA class II antigens, we analyzed thyroid function using anti-thyroid antibodies and HLA-DQ-A and -DQ-B polymorphisms in 69 patients with type 1 DM, in 75 normal healthy controls, and in 21 patients with AITD but without type 1 DM. Eighteen patients (26%) in the diabetic patients had AITD. In the diabetic patients, DQA1*0301 and DQB1*0302 occurred more frequently than in controls [DQA1*0301: OR=1.939, 95% CI=1.210-3.109 ( P =0.008, P c (corrected P ) <0.05); DQB1*0302: OR=2.558, 95% CI=1.354-4.832 ( P =0.005, P c >0.05 )]. Compared with controls, non-diabetic subjects with AITD showed higher frequency of DQA1*0301 ( P c <0.05) and DQB1*0601 ( P c >0.05), but these alleles were not contributing factors in the development of AITD in diabetic patients. In diabetic patients, DQB1*0201, known as susceptible allele of type 1 DM was not a contributing factor in the development of AITD in diabetic patients. Unlike DQB1*0201, DQB1*0401 was more frequently found in diabetic patients with AITD than in controls [ OR=4.053, 95% CI=1.607-10.221 ( P =0.0017, P c <0.05 )] or than in non-diabetic AITD patients [ OR=15.769, 95% CI=1.905-130.530 ( P =0.002, P c <0.05 )]. In non-diabetic subjects, DQB1*0401 did not provide susceptibility for AITD. Our results suggest that HLA DQB1*0401 is a predisposing genetic marker for the development of AITD in patients with type 1 DM in Korea.