Kawasaki disease (KD) is an acute systemic vasculitis that is most seriously complicated by coronary artery aneurysm (CAA). The polymorphisms of platelet endothelial aggregation receptor 1 (PEAR1), notably rs12041331 and rs12566888, were found to be closely related to cardiac disease. However, little is known regarding the connection between PEAR1 and KD. In this study, we genotyped PEAR1 rs12566888 and rs12041331 in 637 healthy infants and 694 KD patients (74 with CAA). Subsequently, odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the strength of their relationships. No significant differences in the frequency of rs12566888 or rs12041331 in PEAR1 were observed between KD and healthy controls. However, regardless of the statistical combination of rs12566888 genotype, the rs12041331 recessive inheritance model was associated with an increased risk of CAA after Bonferroni correction (for rs12041331, AA vs. GG/GA: adjusted OR = 2.37, 95% CI = 1.41-4.01, P = 0.009; combination of two recessive genotypes vs. combination of 0-1 recessive genotypes: adjusted OR = 2.39, 95% CI = 1.42-4.04, P = 0.009). This study suggests for the first time that PEAR1 polymorphisms did not indicate susceptibility for KD occurrence but the rs12041331 polymorphism was associated with increased risk of CAA formation in KD, and the functions of the gene warrant further research.

Background Kawasaki disease (KD) is an acute vasculitis disease that commonly causes acquired heart disease in children. Coronary artery aneurysm (CAA) is a major complication of KD. However, the pathogenesis of KD remains unclear. The results of a genome-wide association study (GWAS) showed that two functional single-nucleotide polymorphisms (SNPs; rs699A>G and rs5050T>G) in the angiotensinogen (AGT) gene were related to cardiovascular disease susceptibility. The purpose of our study was to estimate the relationship between the two GWAS-identified AGT gene polymorphisms and the risk of CAA in Southern Chinese children with KD. Methods We genotyped the two AGT gene polymorphisms (rs699A>G and rs5050T>G) in 760 KD cases and 972 healthy controls. We used the odds ratios (ORs) and 95% confidence intervals (CIs) to estimate the degree of the associations. Results These two AGT gene polymorphisms were not associated with a risk of KD relative to the controls, but after adjusting for sex and age, the carriers of the rs5050G allele with TG/GG vs TT had an adjusted OR = 1.56, 95% CI = 1.01-2.41, and P = 0.044 relative to the carriers of the rs5050TT genotype. The susceptibility to CAA was more predominant in KD patients younger than 12 months old. Conclusions Our results indicate that the AGT gene polymorphism rs5050T>G may increase the risk of CAA in children with KD, especially those who are younger than 12 months. These results need to be verified by a validation study with a larger sample size.