The Role Of ANXA1 On Coronary Artery Lesion And Study On The Methylation Levels Of CTRP1 Promoter Region In Kawasaki Disease

BackgroundKawasaki disease(KD)is an acute and systemic vasculitis whose etiology remains unclear.The most crucial complication is the formation of coronary artery aneurysm(CAA).Annexin A1(ANXA1)is an endogenous antiinflammatory agent and pro-resolving mediator involved in inflammationrelated diseases.Besides,our previous research found that serum CTRP1 levels were significantly increased in KD patients,referring to other methylation studies on KD,we proposed that the up-regulated of serum CTRP1 level might also related to the different methylation levels of CTRP1 promoter regions.This study sought to investigate the relationship between ANXA1 and coronary artery lesion in KD and determined the methylation levels of CTRP1 promoter regions.Methods(1)Serum samples were collected from KD patients and healthy controls(HCs).KD patients were further divided into two groups: KD with CAAs(KD-CAAs)and KD non-CAAs(KD-NCAAs).Serum levels of ANXA1 and interleukin-6(IL-6)were determined using enzyme-linked immunosorbent assays.(2)Whole blood samples of KD and normal children were collected.We extracted DNA from the blood samples and determined the methylation levels of CTRP1 promoter regions using Methyl Target sequencing.ROC analysis was performed to verify the potential of it to predict the formation of CAA in KD.Results(1)Serum ANXA1 levels in the KD group were significantly lower than in the HC group.In particular,serum ANXA1 levels were substantially lower in the KD-CAA groups.Moreover,serum ANXA1 levels were positively correlated with N%,C-reactive protein(CRP),IL-6,FIB,D-dimer but negatively correlated with L% in the KD group.(2)19 CpG islands were found in CTRP1 promoter regions.All of the CpG sites were Hypomethylated in KD patients with site 34,51,69,79,176 and 206 were significantly lower in methylation levels.Moreover,site 69 and 154 were strongly related to the CAA,and possessed the potential to predict the formation of CAA Conclusions(1)ANXA1 might be involved in the development of KD as a protective factor,and might relate to the formation of CAA.(2)The up-regulated of serum CTRP1 levels might due to the hypomethylation of CTRP1 promoter regions.And CpG sites of 69,154 were strongly related to the occurrence of CAA.