Published online August 18, 2008
PEDIATRICS (doi:10.1542/peds.2008-0646)
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ARTICLE

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

Yiu-fai Cheung, MDa, Guo-ying Huang, MDb, Shu-bao Chen, MDc, Xiao-qin Liu, MDb, Li Xi, MDb, Xue-cun Liang, MDb, Mei-rong Huang, MDc, Sun Chen, MDc, Li-su Huang, MDc, Xiao-qing Liu, MDc, Koon-wing Chan, MPhila and Yu-lung Lau, MDa

a Department of Pediatrics and Adolescent Medicine, University of Hong Kong, Hong Kong SAR, China
b Pediatric Cardiovascular Center, Children's Hospital, Fudan University, Shanghai, China
c Shanghai Children Medical Center, Jiao Tong University, Shanghai, China

OBJECTIVE. We tested the hypothesis that single-nucleotide polymorphisms of inflammatory genes C-reactive protein (CRP) and tumor necrosis factor {alpha} (TNF-{alpha}) may exert influence on susceptibility to Kawasaki disease and its arterial sequelae.

METHODS. We analyzed the CRP +1444 C->T and TNF-{alpha} –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-{alpha} –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-{alpha} –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-{alpha} –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-{alpha} –308 A allele carrier as a determinant of only intima-media thickness.

CONCLUSIONS. Our findings suggest that CRP +1444 C->T and TNF-{alpha} –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.

Key Words: gene polymorphisms • Kawasaki disease • arteries

Abbreviations: KD—Kawasaki disease • IMT—intima-media thickness • CRP—C-reactive protein • TNF-{alpha}—tumor necrosis factor {alpha} • SNP—single-nucleotide polymorphism • HDL—high-density lipoprotein • LDL—low-density lipoprotein • SBP—systolic blood pressure • DBP—diastolic blood pressure • PCR—polymerase chain reaction • OR—odds ratio • CI—confidence interval

Accepted Apr 18, 2008.