High mobility group box 1 gene polymorphism in Kawasaki disease

Abstract

Kawasaki disease (KD) is an acute systemic vasculitis of unknown etiology that affects infants and young children. High mobility group box 1 (HMGB1) is a damage-associated molecular pattern (DAMP) molecule that is implicated in the pathogenesis of many inflammatory diseases. Recent reports of elevated serum HMGB1 level during the acute phase of KD and its relationship to poor-response to intravenous immunoglobulin (IVIG) treatment suggest a possible association of HMGB1 polymorphisms with KD. Whole genome sequencing of the HMGB1 gene was performed to identify causative variants. Two tagging single nucleotide polymorphisms (SNPs) of the HMGB1 gene (rs1412125 and rs117077167) were selected using linkage disequilibrium analysis. The tagging SNPs were genotyped using the TaqMan Allelic Discrimination assay in a total of 468 subjects (265 KD patients and 203 controls). Susceptibility, coronary artery lesions (CAL), and IVIG treatment response of KD were then analyzed with HMBG1 genetic variations. The HMGB1 SNPs were not associated with KD susceptibility. However, in KD patients, there was a significant association of rs1412125 with CAL formation in the recessive model (GG vs. AA + GA: OR = 4.98, 95% CI = 1.69–14.66, P = 0.005). In addition, rs1412125 was associated with IVIG resistance in the recessive (GG vs. AA + GA: OR = 4.11, 95% CI = 1.38–12.23, P = 0.017) and allelic models (G vs. A: OR = 1.80, 95% CI = 1.06–3.06, P = 0.027). The rs1412125 in HMGB1 might be a relevant risk factor for the development of CAL and IVIG resistance in KD patients.