Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
College of Medicine and Forensic, Health Science Center of Xi'an Jiao Tong University, Xi'an, Shaanxi, China.
Immun Inflamm Dis. 2020 Dec;8(4):695-703. doi: 10.1002/iid3.359. Epub 2020 Oct 5.
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-B27:05, HLA-B38:02, and HLA-DRB1*08:03 genetic variation and six single nucleotide polymorphisms (SNPs) in MICA genes.
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.
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.
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.
格雷夫斯病（GD）是一种临床自身免疫性甲状腺疾病。在 GD 的治疗过程中，抗甲状腺药物引起的粒细胞缺乏症（TIA）是一种常见且甚至危及生命的药物不良反应。先前的研究表明，TIA 的易感性与 HLA-B27:05、HLA-B38:02 和 HLA-DRB1*08:03 遗传变异以及 MICA 基因中的 6 个单核苷酸多态性（SNP）密切相关。
本研究旨在进一步研究 TIA、HLA-B 和 MICA 之间的关联。
我们对 41 例 TIA 患者和 308 例 GD 对照患者的 MICA-STR 和 MICA-129 变体进行了基因分型，并研究了 SNP 和 MICA 及 HLA-B 等位基因短串联重复（STR）之间的连锁效应。
结果表明，MICA*A5.1 与 TIA 显著相关（p=0.007，优势比=1.958，95%置信区间，1.192-3.214）。此外，还检测到 MICA-129 与六个 SNP 和 HLA-B 之间的高连锁，并且两个单倍型（AAAACAAAAACGGCCTA 和 AACAAAAAAAACATTAA（p=5.14E-07 和 p=3.42E-08，分别））与 TIA 显著相关。此外，当我们仅分析 MICA-129 和 HLA-B 时，发现单倍型（与 p=2.49E-07 的 AAAACAAAAAA 和与 p=2.14E-09 的 AACAAAAAAAA）具有更显著的效果。MICA-129 与六个 SNP 完全连锁，与 TIA 显著相关的单倍型为 ACATTACA（p=2.05E-05）。
这些数据表明 MICA-129 与其他等位基因之间存在显著的连锁效应，表明它们作为 TIA 发展的危险因素具有相互作用。
