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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.

Association of HLA-B and HLA-DRB1 polymorphisms with antithyroid drug-induced agranulocytosis in a Han population from northern China