title: Association of VEGF-1499C-->T polymorphism with diabetic nephropathy in type 1 diabetes mellitus.
abstract: Vascular endothelial growth factor (VEGF) is reported to be implicated in the development of diabetic nephropathy. We performed a case-control study to determine if VEGF-2578C-->A, VEGF-1499C-->T, and VEGF-635G-->C single-nucleotide polymorphisms (SNPs) in the VEGF gene are associated with predisposition to diabetic nephropathy in type 1 diabetes. Genomic DNA was obtained from Irish type 1 diabetic individuals with nephropathy (cases, n=242) and those without nephropathy (controls, n=301), in addition to 400 healthy control samples. These samples were genotyped for the three SNPs using TaqMan or Pyrosequencing technology. Chi-squared analyses revealed no significant differences in genotype or allele frequencies in cases versus controls for VEGF-2578C-->A (genotype, P=.58; allele, P=.52) and VEGF-635G-->C (genotype, P=.58; allele, P=.33). However, a positive association with diabetic nephropathy was observed for the VEGF-1499T allele in the Northern Ireland population (P <.001) and subsequently replicated in a separate population from the Republic of Ireland (P <.001; combined, P <.001). Carriage of the VEGF-1499T allele was associated with a twofold excess risk of developing diabetic nephropathy (OR=2.24, 95% CI=1.50-3.36, P <.0001). No significant differences were found between the healthy control population and the type 1 diabetic population. Our results suggest that the VEGF-1499T allele, or an allele in linkage disequilibrium with this allele, is associated with susceptibility to diabetic nephropathy in the Irish population.
authors.affiliation: Nephrology Research Group, Queen's University of Belfast, Belfast, UK. a.j.mcknight@qub.ac.uk
authors.forename: Amy-Jayne
authors.initials: AJ
authors.lastname: McKnight
authors.forename: A Peter
authors.initials: AP
authors.lastname: Maxwell
authors.forename: Chris C
authors.initials: CC
authors.lastname: Patterson
authors.forename: Hugh R
authors.initials: HR
authors.lastname: Brady
authors.forename: David A
authors.initials: DA
authors.lastname: Savage
mesh_terms: D000293:Adolescent; D000483:Alleles; D016022:Case-Control Studies; D003562:Cytidine / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013936:Thymidine / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D003562:Cytidine; D013936:Thymidine