Inflammatory gene polymorphisms and susceptibility to kawasaki disease and its arterial sequelae.

Authors: Cheung, YF  Huang, GY  Chen, SB  Liu, XQ  Xi, L  Liang, XC  Huang, MR  Chen, S  Huang, LS  Liu, XQ  Chan, KW  Lau, YL 
Citation: Cheung YF, etal., Pediatrics. 2008 Sep;122(3):e608-14. doi: 10.1542/peds.2008-0646. Epub 2008 Aug 18.
Pubmed: (View Article at PubMed) PMID:18710885
DOI: Full-text: DOI:10.1542/peds.2008-0646

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.

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CRRD Object Information
CRRD ID: 9495921
Created: 2014-09-17
Species: All species
Last Modified: 2014-09-17
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.