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Associations of the HMGB1 rs1412125 and rs2249825 polymorphisms with Kawasaki disease

Published online by Cambridge University Press:  23 October 2024

Yeyi Yang Open the ORCID record for Yeyi Yang [Opens in a new window] ,
Ting Zhou ,
Yezhen Yang  and
Zuocheng Yang
Yeyi Yang
Affiliation:
Department of Nephropathy and Rheumatology, the Third Xiangya Hospital of Central South University, Changsha, Hunan, P.R. China
Ting Zhou
Affiliation:
Department of Pediatrics, Zhuzhou Central Hospital, Zhuzhou, Hunan, P.R. China
Yezhen Yang
Affiliation:
Department of Ophthalmology, the Third Xiangya Hospital of Central South University, Changsha, Hunan, P.R. China
Zuocheng Yang*
Affiliation:
Department of Pediatrics, the Third Xiangya Hospital of Central South University, Changsha, Hunan, P.R. China
*
Corresponding author: Zuocheng Yang; Email: [email protected]
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Abstract

Background:

Kawasaki disease is an acute febrile disease causing systemic vasculitis that is common in infants and young children. This study was conducted to explore the relationships of the rs1412125, and rs2249825 single nucleotide polymorphisms of the high mobility group box 1 gene to Kawasaki disease and its complication of coronary artery injury.

Methods:

In total, 200 children with Kawasaki disease (49 with coronary artery injury) and 200 healthy controls were enrolled in this study. Polymerase chain reaction was used to amplify the target gene, and direct sequencing was performed to determine distributions at the rs1412125 T/C and rs2249825 C/G loci in the HMGB1 gene. The chi-squared test was used to compare data between groups. Linkage disequilibrium coefficients and single nucleotide polymorphism haplotype analysis were conducted, and a false-positive report probability analysis was used to assess significant associations. Expression quantitative trait loci analysis was performed to determine if single nucleotide polymorphisms affected mRNA levels via the GTEx portal.

Results:

Significant differences in the genotype TT, TC, and CC distributions (χ2 = 7.918, P = 0.019) and allele T and C frequencies (χ2 = 6.125, P = 0.013) of rs1412125 T/C locus were found between the Kawasaki disease and healthy control groups. The genotype CC was associated with a greater Kawasaki disease risk [odds ratio = 3.205, 95% confidence interval = 1.352–7.595, χ2 = 7.560, P = 0.006]. C allele carriers had a higher Kawasaki disease risk than did T allele carriers (odds ratio = 1.469, 95% confidence interval = 1.083–1.993, χ2 = 6.125, P = 0.013). The rs1412125 genotype T/C distribution (χ2 = 10.906, P = 0.004) and allele frequencies (χ2 = 8.813, P = 0.003) differed significantly between patients with and without coronary artery injury. In the dominant model, the coronary artery injury risk was 3.006 times greater for patients with the TT genotype than for those with the other genotypes (odds ratio = 3.006, 95% confidence interval = 1.540–5.867, χ2 = 10.875, P = 0.001). No significant difference in the rs2249825 genotype C/G distribution or allele frequencies was found between the Kawasaki disease and control groups, or between the coronary artery injury and without coronary artery injury groups.

Conclusions:

The rs1412125 polymorphism of the HMGB1 gene is associated with Kawasaki disease and its coronary artery injury complication. The CC genotype may be a risk factor for Kawasaki disease onset, and the TT genotype may be a risk factor for coronary artery injury in Kawasaki disease.

Keywords

Kawasaki diseasegene polymorphismHMGB1 gene
Type
Original Article
Information
Cardiology in the Young , Volume 34 , Issue 11 , November 2024 , pp. 2296 - 2302
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Copyright
© The Author(s), 2024. Published by Cambridge University Press

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