Inflammatory Gene Polymorphisms and Susceptibility to Kawasaki Disease and Its Arterial Sequelae

Abstract

OBJECTIVE. We tested the hypothesis that single-nucleotide polymorphisms of inflammatory genes C-reactive protein (CRP) and tumor necrosis factor α (TNF-α) may exert influence on susceptibility to Kawasaki disease and its arterial sequelae. METHODS. We analyzed the CRP +1444 C→T and TNF-α −308 G→A polymorphisms in 167 patients aged 8.9 ± 4.1 years with a history of Kawasaki disease (73 with and 94 without coronary aneurysms) and 124 healthy control subjects. For patients with Kawasaki disease, we further determined whether these single-nucleotide polymorphisms were associated with coronary aneurysms, carotid arterial stiffening, and intima-media thickness. RESULTS. Genotypic and allelic frequencies of CRP +1444 for T carrier and TNF-α −308 for A carrier were significantly higher in patients than in control subjects. The genotypic and allelic distributions did not differ between patients with and those without coronary aneurysms; however, patients with CRP +1444 CT/TT genotype compared with those with a CC genotype and patients with TNF-α −308 GA/AA genotype compared with those with a GG genotype had significantly greater carotid arterial stiffness and intima-media thickness. Carriers of both CRP +1444 T allele and TNF-α −308 A allele had the highest susceptibility to Kawasaki disease and a significant trend of increased arterial stiffness and intima-media thickness compared with those who carried either 1 or none of the rare alleles. Multiple linear regression analysis identified CRP +1444 allele carrier as a significant determinant of both carotid stiffness and carotid intima-media thickness and TNF-α −308 A allele carrier as a determinant of only intima-media thickness. CONCLUSIONS. Our findings suggest that CRP +1444 C→T and TNF-α −308 G→A polymorphisms are associated with predisposition to Kawasaki disease and, in patients with Kawasaki disease, increased carotid arterial stiffness and intima-media thickness in the long-term.