Mica Polymorphisms Associated With Antithyroid Drug-Induced Agranulocytosis In The Chinese Han Population

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) inMICAgenes.Aims: The purpose of this study is to further study the associations between TIA, HLA-B andMICA.Materials & Methods: We genotypedMICA-STR andMICA-129variants in 41 TIA and 308 control patients with GD and investigated the linkage effect among SNPs and short tandem repeat (STR) ofMICAand HLA-B alleles.Results: The results showed thatMICA*A5.1was significantly associated with TIA (p = .007, odd ratio = 1.958, 95% confidence interval, 1.192-3.214). In addition, high linkage amongMICA-129and six SNPsMICAand HLA-B was detected, and two haplotypes (AAAACAAAAACGGCCTA and AACAAAAAAAACATTAA (p = 5.14E-07 andp = 3.42E-08, respectively)) were significantly associated with TIA. Furthermore, when we analyzed onlyMICA-129and HLA-B separately, the haplotypes (AAAACAAAAAA withp = 2.49E-07 and AACAAAAAAAA withp = 2.14E-09) were identified with more significant effects.MICA-129was 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 betweenMICA-129and other alleles, suggesting that they exert interactive effects as risk factors for the development of TIA.