Breunis W B, Biezeveld M H, Geissler J, Ottenkamp J, Kuipers I M, Lam J, Hutchinson A, Welch R, Chanock S J, Kuijpers T W
Emma Children's Hospital, Academic Medical Center, and Sanquin Research Institute at the Central Laboratory of the Blood Transfusion Service, University of Amsterdam, Amsterdam, The Netherlands.
Arthritis Rheum. 2006 May;54(5):1588-94. doi: 10.1002/art.21811.
To investigate whether common genetic variants in the vascular endothelial growth factor (VEGF) gene are associated with Kawasaki disease (KD) and the subsequent development of coronary artery lesions.
Common genetic variants in the VEGF gene were analyzed in an association study in a Dutch cohort of 170 KD patients and 300 healthy Dutch Caucasian controls. Genotyping was done with 5'-nuclease TaqMan assays and 3'-hybridization-triggered fluorescence minor groove binder Eclipse assays.
An association with susceptibility to KD was observed with 2 of the 6 single-nucleotide polymorphisms analyzed in VEGF: -2594 A>C (rs699947) and the 236 bp 3' of STP C>T (rs3025039). Also for an 18-bp deletion in the promoter of VEGF a significant difference in the genotype and allele frequencies was observed between the KD patients and the controls. The haplotype CGCC (based on rs699947, rs2010963, rs25648, and rs3025039) was significantly associated with the development of KD (hap score 3.8; P = 0.0002). VEGF plasma levels were significantly higher in patients with the early phase of KD than in the healthy controls, and there was a trend toward higher VEGF plasma levels in KD patients with the -2594 CC and 236 bp 3' of STP CC genotypes.
Our results suggest that polymorphisms of the VEGF gene may play a role in the pathogenesis of KD.
研究血管内皮生长因子（VEGF）基因的常见基因变异是否与川崎病（KD）及随后的冠状动脉病变发展相关。
在一项关联研究中，对荷兰一个队列中的170例KD患者和300名健康的荷兰白种人对照进行VEGF基因常见基因变异分析。采用5'-核酸酶TaqMan分析和3'-杂交触发荧光小沟结合剂Eclipse分析进行基因分型。
在所分析的VEGF基因的6个单核苷酸多态性中，有2个与KD易感性相关：-2594 A>C（rs699947）和STP 3'端236 bp处的C>T（rs3025039）。此外，对于VEGF启动子中的18 bp缺失，KD患者与对照组之间在基因型和等位基因频率上存在显著差异。单倍型CGCC（基于rs699947、rs2010963、rs25648和rs3025039）与KD的发生显著相关（单倍型评分3.8；P = 0.0002）。KD早期患者的VEGF血浆水平显著高于健康对照组，并且-2594 CC和STP 3'端236 bp CC基因型的KD患者有VEGF血浆水平升高的趋势。
我们的结果表明，VEGF基因多态性可能在KD的发病机制中起作用。
