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

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 theHLA-BandHLA-DRB1loci 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) andHLA-DRB1*08:03(P = 1.57 × 10−3) were susceptibility HLA variants for ATD-induced agranulocytosis. All subjects carrying theHLA-B*27:05allele had agranulocytosis. The odds ratios (ORs) comparing allele carriers to non-carriers were 66.24 (95% confidence interval (CI): 3.54–1239.66) forHLA-B*27:05, 7.525 (95% CI: 2.294–24.68) forHLA-B*38:02and 4.316 (95% CI: 1.56–11.93) forHLA-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 orHLA-B*38:02showed lower minimum granulocyte counts than non-carriers (P = 4.74 × 10−4and P = 7.39 × 10−4, respectively). Our findings support the association between genetic variations ofHLA-BandHLA-DRB1with ATD-induced agranulocytosis in a Han population from northern China.