HMGB1 gene polymorphism is associated with coronary artery lesions and intravenous immunoglobulin resistance in Kawasaki disease

• Published in: Rheumatology (Oxford, England) Vol. 58; no. 5; pp. 770 - 775
• Main Authors: Ahn, Jong Gyun, Bae, Yoonsun, Shin, Dongjik, Nam, Jiho, Kim, Kyu Yeun, Kim, Dong Soo
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.05.2019
• Subjects: Alleles; Case-Control Studies; Child, Preschool; Coronary Vessels - pathology; Female; Genetic Predisposition to Disease - genetics; Genotype; HMGB1 Protein - blood; Humans; Immunoglobulins, Intravenous - genetics; Infant; Linkage Disequilibrium; Male; Mucocutaneous Lymph Node Syndrome - drug therapy; Mucocutaneous Lymph Node Syndrome - genetics; Mucocutaneous Lymph Node Syndrome - pathology; Odds Ratio; Polymorphism, Single Nucleotide - genetics; Risk Factors; Treatment Outcome; Whole Genome Sequencing; IVIG resistance; coronary artery lesion; Kawasaki disease; HMGB1
• ISSN: 1462-0324; 1462-0332; 1462-0332
• DOI: 10.1093/rheumatology/key356

Abstract Objectives Kawasaki disease (KD) is an acute systemic vasculitis of unknown aetiology that affects infants and young children. Recent reports of elevated serum high mobility group box 1 (HMGB1) level during the acute phase of KD and its relationship to poor response to IVIG treatment suggest a possible association of HMGB1 polymorphisms with KD. We investigated the association between the polymorphisms of the HMGB1 gene, KD susceptibility, coronary artery lesions, and KD response to IVIG treatment. Methods Whole genome sequencing of the HMGB1 gene was performed to identify causative variants. Two tagging single nucleotide polymorphisms of the HMGB1 gene were selected using linkage disequilibrium analysis. The tagging single nucleotide polymorphisms were genotyped using the TaqMan Allelic Discrimination assay in a total of 468 subjects (265 KD patients and 203 controls). Results The HMGB1 single nucleotide polymorphisms were not associated with KD susceptibility. However, in KD patients, there was a significant association of rs1412125 with coronary artery lesions formation in the recessive model (GG vs AA + GA: odds ratio = 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: odds ratio = 4.11, 95% CI = 1.38-12.23, P = 0.017) and allelic models (G vs A: odds ratio = 1.80, 95% CI = 1.06-3.06, P = 0.027). Conclusion The rs1412125 in HMGB1 might be a risk factor for the development of coronary artery lesions and IVIG resistance in KD patients.