title: Association of age-related macular degeneration with polymorphisms in vascular endothelial growth factor and its receptor.
abstract: OBJECTIVE
  To analyze the association between age-related macular degeneration (AMD) and polymorphisms in vascular endothelial growth factor (VEGF) and VEGF receptor KDR gene polymorphisms. A complex, multifactorial disease in which genetic and environmental factors interact, AMD is the leading cause of blindness in the elderly. Vascular endothelial growth factor (VEGF), a key regulator of angiogenesis, is considered an important factor for the pathogenetic processes of AMD. Previous studies investigated the possible association between VEGF-A gene polymorphisms and AMD, with contrasting data. No study examined the possible role of VEGF receptor KDR gene polymorphisms.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  We enrolled 226 AMD cases and 248 controls from an ophthalmology hospital center.
  
  
  METHODS
  Genotypying for 16 polymorphic markers (single nucleotide polymorphisms [SNPs]) in VEGF-A and KDR genes.
  
  
  METHODS
  Distribution of genotypes in AMD cases and controls.
  
  
  RESULTS
  Two polymorphisms (rs833069 in intron 2 of the VEGF-A gene, rs2071559 in the promoter of the KDR gene) were significantly associated with risk of AMD. In particular, for VEGF-A rs833069 the AMD risk was increased >5-fold for G homozygotes compared with homozygous carriage of the A allele. For KDR rs2071559 the AMD risk was increased >3-fold for T homozygotes compared with homozygous carriage of the C allele. Carriers of risk alleles for both markers have a >6-fold increased risk of AMD with respect to carriers of non-risk alleles.
  
  
  CONCLUSIONS
  We expand previous data on the association of AMD with VEGF-A gene variations and identify for the first time an association with variations in the KDR gene. Because the SNP-604T-bearing KDR promoter has higher transcription activity, our findings further support the role of the VEGF pathway in the pathophysiology of AMD. It is possible that applications of haplotype/genotype analysis in these genes will play a role in risk assessment and pharmacogenomic approaches to AMD diagnosis and management.
authors.affiliation: S. Antonio Hospital, Department of Ophthalmology, Padova, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Galan
authors.forename: Alberto
authors.initials: A
authors.lastname: Ferlin
authors.forename: Luigi
authors.initials: L
authors.lastname: Caretti
authors.forename: Genny
authors.initials: G
authors.lastname: Buson
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sato
authors.forename: Anna Chiara
authors.initials: AC
authors.lastname: Frigo
authors.forename: Carlo
authors.initials: C
authors.lastname: Foresta
mesh_terms: D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007438:Introns / Q000235:genetics; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2