Hamideh Ghazizadeh1, Amir Avan2, Mohammad Fazilati3, Mohsen Azimi-Nezhad4, Maryam Tayefi5, Faezeh Ghasemi6, Mehrane Mehramiz2, Mohsen Moohebati2, Mahmoud Ebrahimi2, Seyed Reza Mirhafez7, Gordon A Ferns8, Habibollah Esmaeili9, Alireza Pasdar10, Majid Ghayour-Mobarhan11. 1. Department of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. 2. Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. 3. Department of Biochemistry, Faculty of Sciences, Payam Noor University, Tehran, Iran. 4. Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; UMR INSERM U 1122, IGE-PCV "Interactions Gène-Environnement en Physiopathologie CardioVasculaire", Université de Lorraine, Nancy F-54000, France; Department of Basic Medical Sciences, Neyshabur University of Medical Sciences, Neyshabur, Iran. 5. Clinical Research Unit, Mashhad University of Medical Sciences, Mashhad, Iran. 6. Department of Biotechnology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran. 7. Department of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Basic Medical Sciences, Neyshabur University of Medical Sciences, Neyshabur, Iran. 8. Brighton & Sussex Medical School, Division of Medical Education, Falmer, Brighton, Sussex BN1 9PH, UK. 9. Department of Biostatistics, School of Health, Mashhad University of Medical Sciences, Mashhad, Iran. 10. Department of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Division of Applied Medicine, Medical School, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK. Electronic address: Pasdara@mums.ac.ir. 11. Department of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: ghayourm@mums.ac.ir.
Abstract
BACKGROUND: Genome-wide association studies (GWAS) have identified common variants at the Vascular-Endothelial-Growth-Factor (VEGF) gene locus, which appear to be associated with plasma VEGF concentrations. These factors are among the major risk factors for cardiovascular disease and metabolic syndrome (MetS). We have investigated the association between serum VEGF concentrations and a VEGF genetic variant (rs6921438 A<G) in 852 patients with or without MetS, defined according to International-Diabetes-Federation (IDF) criteria, recruited from the Mashhad Stroke and Heart Atherosclerotic Disorders cohort and their possible relationships with cardio-metabolic risk-factors and diet. METHODS: In total of 852 individuals, genotyping was performed using polymerase-chain-reaction and restriction-fragment-length-polymorphisms. Serum VEGF level was determined in 122 subjects using the EV 3513 cytokine biochip array. Anthropometric and biochemical characteristics, including fasting blood glucose and lipid profile evaluated by univariate and multivariate analyses. The association of the polymorphism with serum VEGF level and its interaction with dietary intake in association with the essential determinants of cardiovascular risk factors were assessed. RESULTS: As would be expected, patients with MetS had markedly higher body mass index, waist-circumference, serum total cholesterol, triglyceride, hs-CRP and blood pressure, and lower concentrations of HDL-C, compared to non-MetS individuals (P < 0.05). The association between the rs6921438 single nucleotide polymorphism (SNP) and the presence of MetS and individual features of MetS were not statistically significant. Interestingly we observed a significant association between high serum VEGF levels with the GG and GA genotypes in the individuals with MetS, compared to the wild-type genotype, which was also associated with dietary fat intake. CONCLUSION: Our findings show an association between a VEGF gene polymorphism with serum VEGF concentrations and dietary fat intake, but there was no association with the presence of MetS.
BACKGROUND: Genome-wide association studies (GWAS) have identified common variants at the Vascular-Endothelial-Growth-Factor (VEGF) gene locus, which appear to be associated with plasma VEGF concentrations. These factors are among the major risk factors for cardiovascular disease and metabolic syndrome (MetS). We have investigated the association between serum VEGF concentrations and a VEGF genetic variant (rs6921438 A<G) in 852 patients with or without MetS, defined according to International-Diabetes-Federation (IDF) criteria, recruited from the Mashhad Stroke and Heart Atherosclerotic Disorders cohort and their possible relationships with cardio-metabolic risk-factors and diet. METHODS: In total of 852 individuals, genotyping was performed using polymerase-chain-reaction and restriction-fragment-length-polymorphisms. Serum VEGF level was determined in 122 subjects using the EV 3513 cytokine biochip array. Anthropometric and biochemical characteristics, including fasting blood glucose and lipid profile evaluated by univariate and multivariate analyses. The association of the polymorphism with serum VEGF level and its interaction with dietary intake in association with the essential determinants of cardiovascular risk factors were assessed. RESULTS: As would be expected, patients with MetS had markedly higher body mass index, waist-circumference, serum total cholesterol, triglyceride, hs-CRP and blood pressure, and lower concentrations of HDL-C, compared to non-MetS individuals (P < 0.05). The association between the rs6921438 single nucleotide polymorphism (SNP) and the presence of MetS and individual features of MetS were not statistically significant. Interestingly we observed a significant association between high serum VEGF levels with the GG and GA genotypes in the individuals with MetS, compared to the wild-type genotype, which was also associated with dietary fat intake. CONCLUSION: Our findings show an association between a VEGF gene polymorphism with serum VEGF concentrations and dietary fat intake, but there was no association with the presence of MetS.