The Montecarlo Exact Fisher Test demonstrated marked differences in all three Loci, DQA1, DQB1, DRB1 (p<0.0001) between AP versus both AITD and controls, as well as between AP type II (Addison's disease as major endocrine component) and AP type III (T1D + AITD).
The HLA-DRB1*15 (pc =0.001), -DQA1*01 (pc =0.001), -DQB1*05 (pc =0.002) and -DQB1*06 (pc =0.002) alleles were significantly less present in PGA compared to monoglandular AITD and controls, thus indicating protective alleles.
Dividing the APS collective into those with Addison's disease (APS type II) and those without Addison's disease but including type 1 diabetes and AITD (APS type III) demonstrated DR3-DQ2/DRB1*04:01-DQ8 as a susceptibility genotype in APS III (Pc<.001), whereas the DR3-DQ2/DRB1*04:04-DQ8 genotype correlated with APS II (Pc<.001).
In conclusion, we found notable differences in the clinical and genetic characteristics of APS3v patients and T1D/AITD(-) patients in the Japanese population, and the differences in the clinical characteristics between the two groups may reflect distinct genetic backgrounds including the HLA DRB1-DQB1 haplotypes and CTLA4 gene polymorphisms.
The frequency of the DRB1*0405-DQB1*0401 haplotype was significantly higher in AITD patients with GAD Ab than in those without GAD Ab and control subjects.
The frequencies of DRB1 1101-DQB1 0301 and DRB1 1501-DQB1 0602 haplotypes were significantly lower in T1D patients with or without AITD than in control subjects.
Furthermore, the association of SUMO4 M55V variant was stronger in type 1 diabetic patients complicated with AITD (OR, 1.62; 95% CI, 1.06-2.47; P = 0.023) and in patients who have neither type 1 diabetes-susceptible class II HLA, DRB1*0405 nor DRB1*0901 (OR, 2.28; 95% CI, 1.34-3.87; P = 0.0018).