The rs7404339 AA Genotype in CDH5 Contributes to Increased Risks of Kawasaki Disease and Coronary Artery Lesions in a Southern Chinese Child Population

Abstract

BackgroundKawasaki disease (KD) is an acute, self-limited febrile illness of unknown cause. And it predominantly affects children <5 years and the main complication is coronary artery lesion (CAL). Studies demonstrated that vascular endothelial cells (VECs) played a very important role in the CAL of KD. VE-cad encoded by CDH5 may exert a relevant role in endothelial cell biology through controlling the cohesion of the intercellular junctions. The pathogenesis of KD remains unclear and genetic factors may increase susceptibility of KD. However, the relationship between CDH5 polymorphisms and KD susceptibility has not been reported before. The present study is aimed at investigating whether the rs7404339 polymorphism in CDH5 is associated with KD susceptibility and CAL in a southern Chinese child population.Methods and ResultsWe recruited 1,335 patients with KD and 1,669 healthy children. Each participant had supplied 2 mL of fresh blood in the clinical biologic bank at our hospital for other studies. Multiplex PCR is used to assess the genotypes of rs7404339 polymorphism in CDH5. According to the results, we found significant correlated relationship between rs7404339 polymorphism in CDH5 and KD susceptibility [AA vs. GG: adjusted odds ratio (OR) = 1.43, 95% confidence interval (CI) = 1.00–2.05; p = 0.0493; recessive model: adjusted OR = 1.44, 95% CI = 1.01–2.06, P = 0.0431]. In further stratified analysis, we found that children younger than 60 months (adjusted OR = 1.46, 95% CI = 1.01–2.10; p = 0.0424) and male (adjusted OR = 1.70, 95% CI = 1.09–2.65; p = 0.0203) with the rs7404339 AA genotype in CDH5 had a higher risk of KD than carriers of the GA/GG genotype. Furthermore, stratification analysis revealed that patients with the rs7404339 AA genotype exhibited the significantly higher onset risk for CAL than carriers of the GA/GG genotype (adjusted age and gender odds ratio = 1.56, 95% CI = 1.01–2.41; P = 0.0433).ConclusionOur results showed that rs7404339 AA genotype in CDH5 is significant associated with KD susceptibility. And children younger than 60 months and male with the rs7404339 AA genotype had a higher risk of KD than carriers with the GA/GG genotype. Furthermore, patients with the rs7404339 AA genotype exhibited a significantly higher risk of CAL complication than carriers of the GA/GG genotype.