Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, The People's Republic of China.
Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, The People's Republic of China.
Sci Rep. 2017 Sep 20;7(1):11950. doi: 10.1038/s41598-017-12350-2.
Antithyroid drug (ATD)-induced agranulocytosis is associated with human leukocyte antigen (HLA) and nearby genes in Southeast Asian and European populations. The susceptibility of the Han population from northern China to ATD-induced agranulocytosis has not been reported. We evaluated the associations of genetic variants at the HLA-B and HLA-DRB1 loci and 32 candidate single nucleotide polymorphisms (SNPs) with agranulocytosis in 29 patients with ATD-induced agranulocytosis and in 140 patients with Graves' disease (GD) as controls. All subjects were of Han descent from northern China. HLA-B27:05 (P = 1.10 × 10), HLA-B38:02 (P = 2.41 × 10) and HLA-DRB108:03 (P = 1.57 × 10) were susceptibility HLA variants for ATD-induced agranulocytosis. All subjects carrying the HLA-B27:05 allele had agranulocytosis. The odds ratios (ORs) comparing allele carriers to non-carriers were 66.24 (95% confidence interval (CI): 3.54-1239.66) for HLA-B27:05, 7.525 (95% CI: 2.294-24.68) for HLA-B38:02 and 4.316 (95% CI: 1.56-11.93) for HLA-DRB108:03. Two SNPs, rs2596487 (OR = 4.196, 95% CI = 2.086-8.441, P = 2.08 × 10) and rs2228391 (OR = 3.621, 95% CI = 1.596-8.217, P = 1.2 × 10), were independently associated with ATD-induced agranulocytosis. Subjects carrying the 'A' allele of rs1811197 or HLA-B38:02 showed lower minimum granulocyte counts than non-carriers (P = 4.74 × 10 and P = 7.39 × 10, respectively). Our findings support the association between genetic variations of HLA-B and HLA-DRB1 with ATD-induced agranulocytosis in a Han population from northern China.
抗甲状腺药物（ATD）诱导的粒细胞缺乏症与东南亚和欧洲人群中的人类白细胞抗原（HLA）和附近基因有关。中国北方汉族人群对 ATD 诱导的粒细胞缺乏症的易感性尚未报道。我们评估了 HLA-B 和 HLA-DRB1 基因座的遗传变异以及 32 个候选单核苷酸多态性（SNP）与 29 例 ATD 诱导的粒细胞缺乏症患者和 140 例格雷夫斯病（GD）患者（对照组）中性粒细胞缺乏症的相关性。所有受试者均为中国北方汉族人。HLA-B27:05（P=1.10×10），HLA-B38:02（P=2.41×10）和 HLA-DRB108:03（P=1.57×10）是 ATD 诱导的中性粒细胞缺乏症的易感 HLA 变体。所有携带 HLA-B27:05 等位基因的患者均出现中性粒细胞缺乏症。与非携带者相比，携带 HLA-B27:05 等位基因的个体的比值比（OR）为 66.24（95%置信区间（CI）：3.54-1239.66），HLA-B38:02 的 OR 为 7.525（95% CI：2.294-24.68），HLA-DRB108:03 的 OR 为 4.316（95% CI：1.56-11.93）。两个 SNP，rs2596487（OR=4.196，95%CI=2.086-8.441，P=2.08×10）和 rs2228391（OR=3.621，95%CI=1.596-8.217，P=1.2×10），与 ATD 诱导的中性粒细胞缺乏症独立相关。携带 rs1811197 或 HLA-B38:02 的‘A’等位基因的个体与非携带者相比，中性粒细胞最低计数较低（P=4.74×10 和 P=7.39×10，分别）。我们的发现支持 HLA-B 和 HLA-DRB1 基因遗传变异与中国北方汉族人群 ATD 诱导的中性粒细胞缺乏症之间的关联。
