Cheung Yiu-Fai, Huang Guo-Ying, Chen Shu-Bao, Liu Xiao-Qin, Xi Li, Liang Xue-Cun, Huang Mei-Rong, Chen Sun, Huang Li-Su, Liu Xiao-Qing, Chan Koon-Wing, Lau Yu-Lung
Grantham Hospital, University of Hong Kong, Division of Pediatric Cardiology, Department of Pediatrics and Adolescent Medicine, 125 Wong Chuk Hang Rd, Hong Kong, China.
Pediatrics. 2008 Sep;122(3):e608-14. doi: 10.1542/peds.2008-0646. Epub 2008 Aug 18.
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.
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.
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.
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.
我们检验了如下假设，即炎症基因C反应蛋白（CRP）和肿瘤坏死因子α（TNF-α）的单核苷酸多态性可能影响川崎病及其动脉后遗症的易感性。
我们分析了167例年龄为8.9±4.1岁、有川崎病病史的患者（73例有冠状动脉瘤，94例无冠状动脉瘤）以及124例健康对照者的CRP +1444 C→T和TNF-α -308 G→A多态性。对于川崎病患者，我们进一步确定这些单核苷酸多态性是否与冠状动脉瘤、颈动脉僵硬和内膜中层厚度相关。
患者中CRP +1444位点T携带者的基因型和等位基因频率以及TNF-α -308位点A携带者的基因型和等位基因频率显著高于对照者。有冠状动脉瘤和无冠状动脉瘤的患者之间，基因型和等位基因分布没有差异；然而，与CC基因型患者相比，CRP +1444 CT/TT基因型患者以及与GG基因型患者相比，TNF-α -308 GA/AA基因型患者的颈动脉僵硬程度和内膜中层厚度显著更高。与携带1个或不携带罕见等位基因的人相比，CRP +1444 T等位基因和TNF-α -308 A等位基因的携带者对川崎病的易感性最高，且动脉僵硬程度和内膜中层厚度有显著增加的趋势。多元线性回归分析确定CRP +1444等位基因携带者是颈动脉僵硬和颈动脉内膜中层厚度的重要决定因素，而TNF-α -308 A等位基因携带者仅是内膜中层厚度的决定因素。
我们的研究结果表明，CRP +1444 C→T和TNF-α -308 G→A多态性与川崎病的易感性相关，并且在川崎病患者中，长期来看会增加颈动脉僵硬程度和内膜中层厚度。
