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. DESIGN: Case-control study. PARTICIPANTS AND CONTROLS: 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. MAIN OUTCOME MEASURES: 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.
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. DESIGN: Case-control study. PARTICIPANTS AND CONTROLS: 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. MAIN OUTCOME MEASURES: 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-Ars833069 the AMD risk was increased >5-fold for G homozygotes compared with homozygous carriage of the A allele. For KDRrs2071559 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: Stephanie A Hagstrom; Gui-shuang Ying; Gayle J T Pauer; Gwen M Sturgill-Short; Jiayan Huang; Maureen G Maguire; Daniel F Martin Journal: JAMA Ophthalmol Date: 2014-05 Impact factor: 7.389
Authors: Luís A Arana; Anderson T Pinto; Gerald J Chader; Jose D Barbosa; Sabina Morales; Ana T Moreira; Mauricio Maia; Mark S Humayun Journal: Graefes Arch Clin Exp Ophthalmol Date: 2012-03-20 Impact factor: 3.117
Authors: Nathan G Lambert; Hanan ElShelmani; Malkit K Singh; Fiona C Mansergh; Michael A Wride; Maximilian Padilla; David Keegan; Ruth E Hogg; Balamurali K Ambati Journal: Prog Retin Eye Res Date: 2016-05-06 Impact factor: 21.198