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

Abstract

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. (Stroke. 2011;42:2393-2402.)

Polymorphisms in VEGFA gene affect the antihypertensive responses to enalapril

“…In fact, the AGG haplotype was showed to express less VEGF than CGG haplotype [41]. Moreover, the AGG haplotype was associated with stroke [42] and affected the ejection fraction in hypertensive patients with left ventricular hypertrophy [25]. Taking these findings into consideration, we could speculate that a reduced VEGF expression could increase the risk for cardiovascular damages in AGG haplotype carriers through mechanisms suggested by experimental studies [16,43].…”

Association between the polymorphisms of the vascular endothelial growth factor gene and metabolic syndrome

“…The CC genotype was also associated with an impaired prognosis in the patients with chronic heart failure (21), the development of heart failure following myocardial infarction (23), AMI (15) and coronary collaterals in the patients with CAD (26) and coronary atherosclerosis (25). The -634 variant genotypes (GC and CC) in the patients with silent brain infarction were significantly lower than those in the controls (24), whereas the G allele of -634G>C polymorphism was significantly higher in the patients with Kawasaki disease with coronary artery lesions (CAL) than in those without CAL or control subjects (32). Moradzadegan et al (33) reported Adjusted by age and gender; b significant difference.…”

“…Total genomic DNA was prepared from whole blood following the lysis of red blood cells. The areas spanning the polymorphic sites of -634G>C in the 5'-untranslated region (UTR) and 936C>T in the 3'-UTR of the VEGF gene were amplified by the polymerase chain reaction from the genomic DNA using primers and reaction conditions described previously (24). The -634G>C and 936C>T polymorphisms were identified following the digestion of amplified DNA with the endonucleases, AvaII and NlaIII, respectively.…”

Association of miR-34a, miR-130a, miR-150 and miR-155 polymorphisms with the risk of ischemic stroke

“…Based on clinical manifestations and neuroimaging data, two neurologists classified ischemic stroke into 3 etiological subtypes using the criteria from the Trial of Org 10172 in Acute Stroke Treatment (TOAST) clinical trial as follows (22): i) subtype 1: LAD, an infarct lesion of ≥15 mm in diameter, as determined by an MRI, and significant (>50%) stenosis of a major brain artery or a branch cortical artery, as determined by cerebral angiography, with symptoms associated with that arterial territory; ii) subtype 2: SVD, an infarct lesion of <15 mm, but >5 mm in diameter, as determined by an MRI, and classic lacunar syndrome without evidence of cerebral cortical dysfunction or a potentially detectable cardiac source for the embolism; and iii) subtype 3: CE, arterial occlusions presumably due to a heart-originated embolus, as detected by cardiac evaluation. We measured clinical parameters, including hypertension, diabetes, hyperlipidemia, homocysteine levels, folate levels, vitamin B12 levels, cholesterol, platelet (PLT) count, PT, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen levels, antithrombin levels, BUN levels and uric acid levels based on previously described methods (23,24).…”