Correlation between inducible nitric oxide synthase gene polymorphism and affectability of Kawasaki disease coincidenced coronary artery lesion

Abstract:

Objective：To investigate the correlation between inducible nitric oxide synthase（iNOS） gene polymorphism and the devel－opment of coronary artery lesion（CAL） in Kawasaki disease（KD）. Methods：Totally 146 patients with KD in the Children’s Hospital in Chongqing Medical University were included as KD group and 119 healthy children at the same period as control group. There were 79 KD patients with CAL as CAL group and 67 patients without CAL as NCAL group. SNPs of iNOS gene loci -1026C/A and +2087G/A were genotyped by using MassARRAY-IPLEX technology and matrix-assisted laser desorption ionization time of flight inass spec－trometry platform（MALDI-TOF-MS）. Relation between gene polymorphisms and the development of CAL in KD were analyzed. Plas－ma iNOS level was determined by ELISA，plasma NO level was measured by nitric acid reductase and expression levels were com－pared between groups. Results：Plasma iNOS level was significantly lower in control group（48.02±31.46） U/L than that in CAL group（90.29±47.68） U/L and NCAL group（81.46±41.32） U/L（P=0.000，0.000）. Plasma NO level was not significantly different be－tween groups（F=3.003，P=0.052）. Frequencies of the A minor allele and GA+AA genotypes of +2087G/A were higher in CAL group than in NCAL group（P=0.010，0.013）；both can significantly reduce the risk of CAL compared with G allele and GG genotype[OR（95%CI）=0.41（0.21-0.82），0.42（0.19-0.92），P=0.010，0.029]. Frequencies of haplotype -1026C/+2087A were different between CAL group and NCAL group（P=0.010）. -1026C/+2087A haplotype was associated with a significantly decreased risk of CAL[OR（95%CI）=0.45（0.22-0.91），P=0.030]. Conclusions：Results suggested that plasma iNOS is important in the development of vasculitis and CAL in KD. iNOS gene +2087G/A polymorphism and its -1026C/+2087A haplotype are associated with the development of CAL in KD. +2087A allele may significantly reduce the risk of CAL by lowering plasma iNOS level and reducing NO production.