HIF1A as a major vascular endothelial growth factor regulator: Do its polymorphisms have an association with age-related macular degeneration?

Background: To investigate the association between age-related macular degeneration (AMD) and the polymorphisms of HIF1A, a major vascular epithelial growth factor regulator under hypoxic conditions. The associations of AMD and polymorphisms of genes CFH, SKIV2L and MYRIP were also studied. Design: Prospective study. Participants: Eighty-seven AMD patients and 80 healthy subjects admitted to the Department of Ophthalmology at Pamukkale University Hospital, Denizli, Turkey, were included: 45 (52%) had wet type AMD, and 42 (48%) had dry type AMD. Methods: Polymorphisms rs1061170 (CFH), rs429608 (SKIV2L), rs2679798 (MYRIP) and both rs11549465 and rs11549467 (HIF1A) were investigated in DNA isolated from peripheral blood samples of the cases and controls by dye-termination DNA sequencing. Main Outcome Measures: Genotype distribution of rs1061170 (CFH), rs429608 (SKIV2L), rs2679798 (MYRIP) and both rs11549465 and rs11549467 (HIF1A) in AMD cases and healthy controls; association between genotypes and AMD subtypes. Results: Given the significant difference between the mean age of case and control groups (72.13±5.77 vs. 62.80±5.22, respectively) (P=.000), subsequent analyses were adjusted for age. We found that having at least one C allele for polymorphism rs1061170 increases AMD risk independent of age (OR=2.42, 95% confidence interval [CI], 1.22-4.81). The ancestral T allele for polymorphism rs1061170 has a protective effect for AMD (OR=0.53, 95% CI, 0.34-0.83). No statistically significant difference for distributions of other single nucleotide polymorphisms (SNPs) emerged between patients and healthy subjects. Conclusions: No associations appeared between HIF1A SNPs and AMD, which were studied here for the first time; however, polymorphism rs1061170 of the CFH gene is associated with AMD in our population. © 2014 Royal Australian and New Zealand College of Ophthalmologists