Clinical Sciences Association Between VEGF Polymorphisms and Homocysteine Levels in Patients With Ischemic Stroke and Silent Brain Infarction

Background and Purpose—Vascular endothelial growth factor (VEGF) plays a role in atherosclerosis-related diseases such as cerebrovascular or cardiovascular diseases. However, the effect of VEGF-2578CϾA,-1154GϾA,-634GϾC, and 936CϾT polymorphisms on the susceptibility to stroke and silent brain infarction has not been reported. Methods—Using polymerase chain reaction-amplified DNA, VEGF polymorphisms were analyzed in 615 patients with ischemic stroke, 376 patients with silent brain infarction, and 494 control subjects. Results—The AA and CCϩCA (C allele bearing) genotype frequencies of the-2578CϾA polymorphism and the CTϩTT (T allele-bearing) genotype frequency of the 936CϾT polymorphism were significantly different between the stroke and control groups (false discovery rate-adjusted probability values of 0.016, 0.044, and 0.044, respectively). When stratified by the size of the occluded vessel, the VEGF polymorphisms were associated with patients with multiple small-artery occlusions. Several haplotypes of the VEGF polymorphisms were significantly different between the control and stroke groups. With respect to silent brain infarction, the difference in the frequency of the-634GϾC polymorphism between the GCϩCC (C allele-bearing) genotype and the controls was marginally significant (false discovery rate-adjusted probability value of 0.056). On the other hand, the-634GϾC and 936CϾT polymorphisms were associated with plasma homocysteine levels of patients with multiple or single small-artery occlusions, respectively. Conclusions—This study suggests that VEGF polymorphisms and haplotypes are possible genetic determinants for the risk of ischemic stroke, particularly in patients with multiple small-artery occlusions. However, VEGF polymorphisms had only a weak association with plasma homocysteine levels in the Korean population.