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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 -2578C>A, -1154G>A, -634G>C, and 936C>T 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 CC+CA (C allele bearing) genotype frequencies of the -2578C>A polymorphism and the CT+TT (T allele-bearing) genotype frequency of the 936C>T 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 -634G>C polymorphism between the GC+CC (C allele-bearing) genotype and the controls was marginally significant (false discovery rate-adjusted probability value of 0.056). On the other hand, the -634G>C and 936C>T 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.