Association of vascular endothelial growth factor (VEGF) and VEGF receptor gene polymorphisms with coronary artery lesions of Kawasaki disease
Association of vascular endothelial growth factor (VEGF) and VEGF receptor gene polymorphisms with coronary artery lesions of Kawasaki disease
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DOI：
10.1203/01.pdr.0000145280.26284.b9
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发表时间：
2004-12-01
影响因子：
3.6
通讯作者：
Hara, T
中科院分区：
文献类型：
--
作者：
Kariyazono, H;Ohno, T;Hara, T
我们分析了日本川崎（KD）患者和正常对照组血管内皮生长因子（VEGF）及其受体[Fms相关酪氨酸激酶-1、激酶插入域受体（KDR）]的遗传多态性，以研究这些基因是否与KD的发生和/或KD冠状动脉病变（CAL）的发展有关。我们发现VEGF g.-G等位基因的频率与正常人相比有显著性差异。634 G>C单核苷酸多态性在伴CAL的KD患者中显著高于无CAL的KD患者（p = 0.012）或对照组（p = 0.021），这是因为伴CAL的KD患者GG基因型频率显著较高。+ KD伴CAL组A1 A1基因型频率显著高于对照组（p = 0.040）和无CAL组（p = 0.013）。多因素分析结果显示，KDR基因A1 A1基因型与临床特征、基因型之间存在显著相关性（P < 0. 05），与KDR基因型之间存在显著相关性（P < 0. 05）。4422（AC）11-14基因多态性是CAL发生的独立危险因素，在几个临床参数中比值比最高（比值比6.76; 95%可信区间1.05-43.48）。双荧光素酶检测结果表明，KDR g.+的A1等位基因与KDR g. 4422（AC）11个重复序列的沉默功能弱于12个AC重复序列的A2等位基因。提示VEGF及其受体KDR基因参与了KD患者CAL的发生。
We analyzed the genetic polymorphisms of vascular endothelial growth factor (VEGF) and its receptors [Fms-related tyrosine kinase-1, kinase insert domain receptor (KDR)] in Japanese patients with Kawasaki disease (KD) and normal control subjects to examine whether these genes would contribute to the KD occurrence and/or the development of coronary artery lesion (CAL) in KD. We found that the frequency of G allele of VEGF g.-634 G>C single-nucleotide polymorphism in the promoter region was significantly higher in KD patients with CAL than in those without CAL (p = 0.012) or control subjects (p = 0.021) because of a significantly higher frequency of the GG genotype in KD patients with CAL. In addition, the frequency of the A1 allele with 11 AC repeats of KDR g. + 4422(AC)11- 14 dinucleotide repeat polymorphism in intron 2 was significantly higher in KD patients with CAL than in those without CAL (p = 0.013) or control subjects (p = 0.040) as a result of a significantly higher frequency of the A1A1 genotype in KD with CAL patients. The multivariate analysis of clinical features and genotypes of the two polymorphisms showed that the A1A1 genotype of KDR g.+4422(AC)11-14 polymorphism was an independent risk factor for the development of CAL with the highest odds ratio among several clinical parameters (odds ratio 6.76; 95% confidence interval 1.05-43.48). Dual luciferase assay demonstrated that the A1 allele with KDR g.+4422(AC)11 repeats showed a weaker silencer function than the A2 allele with 12 AC repeats. These findings suggested that VEGF and its receptor, KDR, genes contributed to the development of CAL in KD patients.