The HLA-DRB1 gene and Graves disease in Taiwanese children: a case-control and family-based study

Graves disease (GD) is an autoimmune thyroid disease with a female preponderance and a wide range of ages at onset, and human leukocyte antigen (HLA) gene plays a primary role in the susceptibility to GD. We aim to investigate the associations between HLA‐DRB1 alleles and Taiwanese children with GD by both case‐control and family‐based studies. A total of 241 unrelated children with GD, 539 healthy controls, 115 trios of affected patients and their parents, and 121 trios of unaffected siblings and their parents were recruited. HLA‐DRB1 genotyping was performed by polymerase chain reaction and sequence‐based typing assays. We found that DRB1*09:01 (OR = 2.60, 95% CI 2.02–3.35, Pc = 6.55 × 10−13) was associated with GD risk, while DRB1*12:02 (OR = 0.32, 95% CI 0.20–0.53, Pc = 4.55 × 10−5) was protective against GD. Transmission/disequilibrium test further confirmed an overtransmission of the DRB1*09:01 (OR 3.37, 95% CI 2.13–6.22, Pc = 1.0 × 10−5) and an undertransmission of the DRB1*12:02 (OR 0.21, 95% CI 0.05–0.42, Pc = 1.7 × 10−3). The findings were similar in females when stratified by gender. In conclusion, our results clearly identify that HLA‐DRB1*09:01 confers susceptibility to GD and DRB1*12:02 exerts protection against GD development in Taiwanese children.