Background: Graves' disease (GD) is a clinical autoimmune thyroid disease. During the treatment of GD, antithyroid drug-induced agranulocytosis (TIA) is a common and even life-threatening adverse drug reaction. Previous studies suggested that susceptibility to TIA is strongly associated with HLA-B*27:05, HLA-B*38:02, and HLA-DRB1*08:03 genetic variation and six single nucleotide polymorphisms (SNPs) in MICA genes.
Aims: The purpose of this study is to further study the associations between TIA, HLA-B and MICA.
Materials & methods: We genotyped MICA-STR and MICA-129 variants in 41 TIA and 308 control patients with GD and investigated the linkage effect among SNPs and short tandem repeat (STR) of MICA and HLA-B alleles.
Results: The results showed that MICA*A5.1 was significantly associated with TIA (p = .007, odd ratio = 1.958, 95% confidence interval, 1.192-3.214). In addition, high linkage among MICA-129 and six SNPs MICA and HLA-B was detected, and two haplotypes (AAAACAAAAACGGCCTA and AACAAAAAAAACATTAA (p = 5.14E-07 and p = 3.42E-08, respectively)) were significantly associated with TIA. Furthermore, when we analyzed only MICA-129 and HLA-B separately, the haplotypes (AAAACAAAAAA with p = 2.49E-07 and AACAAAAAAAA with p = 2.14E-09) were identified with more significant effects. MICA-129 was completely linked to six SNPs with haplotypes ACATTACA (p = 2.05E-05) significantly associated with TIA.
Conclusion: These data indicated that there was a significant linkage effect between MICA-129 and other alleles, suggesting that they exert interactive effects as risk factors for the development of TIA.
Keywords: ATD-induced agranulocytosis; Graves' disease; MICA; STR; association.
© 2020 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.