<i>HLA‐DRB1*15:01</i> Is Associated and Linked With Kawasaki Disease, With <i>DRB1*14:01</i> Conferring Risk to Coronary Artery Lesions: Case‐Control and Family‐Based Studies

Kawasaki disease (KD), also known as mucocutaneous lymph node syndrome, is a leading cause of vasculitis in children aged < 5 years. The HLA complex has been investigated for its association with KD since 1978 without conclusive results due to limitations such as small sample sizes. This study aimed to evaluate the associations and genetic linkage between HLA-DRB1 and KD, as well as its complications. The case-control and family-based studies enrolled 795 patients with KD and 946 healthy controls. Of the 795 patients, 180 trios were included. Genotypes of HLA-DRB1 were identified by sequence-based typing according to the International ImMunoGeneTics database. Allele frequencies were calculated using PyPop 7.0. The transmission/disequilibrium test (TDT) was used to verify the genetic linkage between HLA-DRB1 and KD. HLA-DRB1*15:01 was significantly associated with KD (OR, 1.44, Pc = 0.03) and with KD without CALs (OR = 1.46, Pc = 0.04). HLA-DRB1*14:01 was a risk factor for KD with CALs (OR = 2.47, Pc = 0.004) whereas HLA-DRB1*12:02 was a protective factor against CALs (OR = 0.49, Pc = 0.01). In the family-based study, HLA-DRB1*15:01 demonstrated significant overtransmission to KD patients (OR = 3.35; 95% CI, 2.20-5.78; Pc = 1.19E-06) and to KD patients without CALs (OR = 4.42; 95% CI, 2.59-10.08; Pc = 6.24E-06). The overtransmission remained significant in male KD patients (OR = 2.81; 95% CI, 1.68-5.58; Pc = 0.003), and in male KD patients without CALs (OR = 3.22; 95% CI, 1.69-8.84; Pc = 0.02). Our study identified significant associations between HLA-DRB1*15:01, *14:01, and *12:02 with KD. The association between HLA-DRB1*15:01 and KD was further verified by TDT, indicating a genetic linkage between the HLA-DRB1 locus and KD susceptibility.