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

Clin Exp Ophthalmol. 2015 Jan-Feb;43(1):47-53. doi: 10.1111/ceo.12376. Epub 2014 Aug 19.

Abstract

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.

Keywords: AMD; CFH; HIF1A; MYRIP; SKIV2L.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Complement Factor H / genetics
  • DNA Helicases / genetics
  • Female
  • Gene Frequency
  • Genotype
  • Geographic Atrophy / genetics*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide*
  • Prospective Studies
  • Sequence Analysis, DNA
  • Vascular Endothelial Growth Factor A / metabolism*
  • Vesicular Transport Proteins / genetics
  • Wet Macular Degeneration / genetics*

Substances

  • CFH protein, human
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • MYRIP protein, human
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Vesicular Transport Proteins
  • Complement Factor H
  • DNA Helicases
  • SKIV2L protein, human