Vascular endothelial growth factor gene haplotypes in Kawasaki disease

Abstract

ObjectiveTo 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.MethodsCommon 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.ResultsAn 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.ConclusionOur results suggest that polymorphisms of the VEGF gene may play a role in the pathogenesis of KD.

Impact of VEGF gene polymorphisms and haplotypes on radiation-induced late toxicity in prostate cancer patients

“…Polymorphisms in the VEGF gene have also been identified with some of them leading to altered activity [1,8,26]. However, the role of VEGF gene variants in the development of late adverse events after radiotherapy is still unclear.…”

Susceptibility genes for Kawasaki disease: toward implementation of personalized medicine

“…30 Although several other groups have studied other combinations of HLA subtypes, no consistent association has been detected so far. Considering that no significant linkage was detected near the 6p region in our genome-wide linkage analysis, 31 34 and MCP-1 35 ), hematopoietins (interleukin-4 (IL-4) [36][37][38] and IL-6 39 ), IL-1 family (IL-1b, 37 IL-18, 40 and IL-1Ra 37 ), IL-10 family (IL-10 41 ), platelet-derived growth factor family (vascular endothelial growth factor (VEGF) [42][43][44][45] and VEGFR2 42 ), and tumor necrosis factor (TNF) family (TNF-a, 46-50 lipoteichoic acid, 47 and CD40L 51,52 ). Other candidates include plasma proteins (C-reactive protein [53][54][55] and MBL2 53,55,56 ), matrix metalloproteinase (MMP) and their inhibitors (MMP2, 58 MMP3, 57,58 MMP-9, 58 MMP-12, 58 MMP-13, 58 and tissue inhibitors of metalloproteinase-2 59 ), enzymes related to atherosclerosis (methylenetetrahydrofolate reductase (MTHFR), 60 endothelial nitric oxide synthase, 61 and inducible nitric oxide synthase 61 ), components of the renin-angiotensin system (angiotensin-converting enzyme [62][63][64][65] and AGTR1 64 ), and an unclassified group (CD14, 66 FCGR2A, 67,68 SLC11A1, 69 PLA2G7, 70 UGT1A1, 71 MICA, 72 and HMOX1 71 ).…”

CASP3 gene single-nucleotide polymorphism (rs72689236) and Kawasaki disease in Taiwanese children

“…Kariyazono et al 30 and Breunis et al 31 reported that the vascular endothelial growth factor gene polymorphism was associated with susceptibility and CAL formation in KD; however, it cannot be verified in the Taiwanese population. 32 Burns et al 33 revealed that interleukin 4 has an important role in KD pathogenesis and disease susceptibility, but the results are different from the studies in the Taiwanese population.…”