The Role of VEGF and KDR Polymorphisms in Moyamoya Disease and Collateral Revascularization

Abstract

We conducted a case-control study to investigate whether vascular endothelial growth factor (VEGF −2578, −1154, −634, and 936) and kinase insert domain containing receptor (KDR −604, 1192, and 1719) polymorphisms are associated with moyamoya disease. Korean patients with moyamoya disease (n = 107, mean age, 20.9±15.9 years; 66.4% female) and 243 healthy control subjects (mean age, 23.0±16.1 years; 56.8% female) were included. The subjects were divided into pediatric and adult groups. Among the 64 surgical patients, we evaluated collateral vessel formation after 2 years and divided patients into good (collateral grade A) or poor (collateral grade B and C) groups. The frequencies and distributions of four VEGF (−2578, −1154, −634, and 936) and KDR (−604, 1192, and 1719) polymorphisms were assessed from patients with moyamoya disease and compared to the control group. No differences were observed in VEGF −2578, −1154, −634, and 936 or KDR −604, 1192, and 1719 polymorphisms between the control group and moyamoya disease group. However, we found the −634CC genotype occurred less frequently in the pediatric moyamoya group (p = 0.040) whereas the KDR −604C/1192A/1719T haplotype increased the risk of pediatric moyamoya (p = 0.024). Patients with the CC genotype of VEGF −634 had better collateral vessel formation after surgery. Our results suggest that the VEGF −634G allele is associated with pediatric moyamoya disease and poor collateral vessel formation.

Vascular endothelial growth factor (VEGF)-related polymorphisms rs10738760 and rs6921438 are not risk factors for proliferative diabetic retinopathy (PDR) in patients with type 2 diabetes mellitus (T2DM)

“…The increase in VEGF gene expression is predominantly mediated by hypoxia-inducible factor-1 (HIF-1) [12]. The human VEGF gene is located on chromosome 6p21.3 and consists of 8 exons separated by 7 introns [21,22]. Single nucleotide polymorphisms (SNPs) of or related to the VEGF gene have been associated with VEGF expression/serum levels [23][24][25][26][27].…”

Promoter polymorphisms of the vascular endothelial growth factor gene are associated with metabolic syndrome susceptibility in Koreans

“…DNA isolated by salt extraction was genotyped by the conventional polymerase chain reaction (PCR) followed by the restriction fragment length polymorphism technique. The primers and reaction conditions for PCR were as described previously (18). Following amplification, the PCR products were digested with restriction enzymes, AvaII and MnlI (New England Biolabs, Inc., Ipswich, MA, USA), for genotyping of the -2578C>A and -1154G>A polymorphisms, respectively.…”

Single Nucleotide Polymorphism in Patients with Moyamoya Disease

“…VEGF binds its receptor tyrosine kinases, VEGF receptor-1 and VEGF receptor-2 [also known as kinase insert domain containing receptor, or kinase insert domain contaning receptor (KDR)] but KDR is the key receptor mediating angiogenesis 71) and is essential for endothelial cell survival and integrity 13) . Park et al 53) found the genotypes including the VEGF-634C allele had better collateral vessel formation after surgery. They suggest that VEGF or KDR polymorphisms influence MMD as well as the formation of synangiosis-induced collateral vessel after bypass surgery.…”