title: 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 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.
authors: Grantham Hospital, University of Hong Kong, Division of Pediatric Cardiology, Department of Pediatrics and Adolescent Medicine, 125 Wong Chuk Hang Rd, Hong Kong, China. xfcheung@hkucc.hku.hk
authors: Yiu-Fai
authors: YF
authors: Cheung
authors: Guo-Ying
authors: GY
authors: Huang
authors: Shu-Bao
authors: SB
authors: Chen
authors: Xiao-Qin
authors: XQ
authors: Liu
authors: Li
authors: L
authors: Xi
authors: Xue-Cun
authors: XC
authors: Liang
authors: Mei-Rong
authors: MR
authors: Huang
authors: Sun
authors: S
authors: Chen
authors: Li-Su
authors: LS
authors: Huang
authors: Xiao-Qing
authors: XQ
authors: Liu
authors: Koon-Wing
authors: KW
authors: Chan
authors: Yu-Lung
authors: YL
authors: Lau
mesh_terms: D000483:Alleles; D002097:C-Reactive Protein / Q000235:genetics* / Q000378:metabolism; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging / Q000503:physiopathology; D002648:Child; D004247:DNA / Q000235:genetics*; D004548:Elasticity; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics*; D014463:Ultrasonography; D014655:Vascular Resistance / Q000502:physiology*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D004247:DNA