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

Abstract

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.