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首页> 美国卫生研究院文献>Scientific Reports >Association of HLA-B and HLA-DRB1 polymorphisms with antithyroid drug-induced agranulocytosis in a Han population from northern China
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Association of HLA-B and HLA-DRB1 polymorphisms with antithyroid drug-induced agranulocytosis in a Han population from northern China

机译：HLA-B和HLA-DRB1基因多态性与中国北方汉族人群抗甲状腺药致粒细胞缺乏症的关系

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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-B*27:05 (P = 1.10 × 10−4), HLA-B*38:02 (P = 2.41 × 10−4) and HLA-DRB1*08:03 (P = 1.57 × 10−3) were susceptibility HLA variants for ATD-induced agranulocytosis. All subjects carrying the HLA-B*27:05 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-B*27:05, 7.525 (95% CI: 2.294–24.68) for HLA-B*38:02 and 4.316 (95% CI: 1.56–11.93) for HLA-DRB1*08:03. Two SNPs, rs2596487 (OR = 4.196, 95% CI = 2.086–8.441, P = 2.08 × 10−5) and rs2228391 (OR = 3.621, 95% CI = 1.596–8.217, P = 1.2 × 10−3), were independently associated with ATD-induced agranulocytosis. Subjects carrying the ‘A’ allele of rs1811197 or HLA-B*38:02 showed lower minimum granulocyte counts than non-carriers (P = 4.74 × 10−4 and P = 7.39 × 10−4, 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.
机译：抗甲状腺药（ATD）诱导的粒细胞缺乏症与东南亚和欧洲人口中的人类白细胞抗原（HLA）和附近的基因有关。尚无中国北方汉族人群对ATD引起的粒细胞缺乏症的报道。我们评估了29例ATD诱发的粒细胞缺乏症患者和140例Graves病（GD）患者中HLA-B和HLA-DRB1位点的遗传变异与32种候选单核苷酸多态性（SNP）与粒细胞缺乏症的关系。所有受试者均为中国北方的汉族人。 HLA-B * 27：05（P = 1.10×10 −4 ），HLA-B * 38：02（P = 2.41×10 −4 ）和HLA- DRB1 * 08：03（P = 1.57×10 -3 ）是ATD诱导的粒细胞缺乏症的易感性HLA变体。所有携带HLA-B * 27：05等位基因的受试者均患有粒细胞缺乏症。 HLA-B * 27：05对等位基因携带者与非携带者进行比较的优势比（OR）为66.24（95％置信区间（CI）：3.54–1239.66），HLA-B *为7.525（95％CI：2.294–24.68）。对于HLA-DRB1 * 08：03，B * 38：02和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 -5 ）和rs2228391（OR = 3.621，95％CI = 1.596–8.217，P = 1.2 ×10 −3 ）与ATD诱导的粒细胞缺乏症独立相关。携带rs1811197或HLA-B * 38：02的'A'等位基因的受试者的最低粒细胞计数低于非携带者（P = 4.74×10 -4 和P = 7.39×10 -4 ）。我们的发现支持了来自中国北方汉族人群的HLA-B和HLA-DRB1遗传变异与ATD诱导的粒细胞缺乏症的关系。

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