Complement factor H and high-temperature requirement A-1 genotypes and treatment response of age-related macular degeneration

Ophthalmology. 2011 Jan;118(1):93-100. doi: 10.1016/j.ophtha.2010.04.007. Epub 2010 Aug 3.

Abstract

Purpose: To determine whether there is an association between complement factor H (CFH), high-temperature requirement A-1 (HTRA1), vascular endothelial growth factor (VEGF), and pigment epithelium-derived factor (PEDF) genotypes and response to treatment with photodynamic therapy (PDT) for age-related macular degeneration (AMD) in a Japanese population.

Design: Prospective, case-control study.

Participants: One hundred ten patients with exudative AMD treated by verteporfin PDT were recruited prospectively at the Department of Ophthalmology, Saitama Medical University Hospital, Saitama, Japan.

Methods: The patients were genotyped for 4 single nucleotide polymorphisms (SNPs; rs800292, rs1061170, rs1410996, rs2274700) in the CFH gene, a rs11200638-SNP in the HTRA1 gene, 3 SNPs (rs699947, rs1570360, rs2010963) in the VEGF gene, and 4 SNPs (rs12150053, rs12948385, rs9913583, rs1136287) in the PEDF gene using a TaqMan assay.

Main outcome measures: The treatment outcomes and genotypes of CFH, HTRA1, VEGF, and PEDF polymorphisms.

Results: Best-corrected visual acuity 1 year after PDT was significantly increased in patients with the HTRA1-rs11200638 GG genotype as compared with patients with the GA or AA genotypes (P = 2.9 × 10⁻², 7.0 × 10⁻⁴, respectively). The rate of recurrence in the 12-month period after PDT was also associated with HTRA1-rs11200638 genotype (P = 3.12 × 10⁻²). Patients with the AA genotype of HTRA1-rs11200638 had an approximately 6-fold greater risk of the recurrence than patients with the GG genotype (P = 5.58 × 10⁻³). Significant differences were demonstrated in the mean time interval from the initial treatment to the time of recurrence for the genotypes of CFH-rs1410996/-rs2274700 (P = 8.50 × 10⁻³).

Conclusions: The HTRA1-rs11200638 and CFH-rs1410996/-rs2274700 variants were associated with response to PDT in this study population. These variants may be used for genetic biomarkers to estimate visual outcomes and recurrences in the response to PDT with significant predictive power.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Complement Factor H / genetics
  • Eye Proteins / genetics
  • Female
  • Genotype
  • High-Temperature Requirement A Serine Peptidase 1
  • Humans
  • Macular Degeneration / drug therapy*
  • Macular Degeneration / genetics*
  • Male
  • Middle Aged
  • Nerve Growth Factors / genetics
  • Photochemotherapy*
  • Photosensitizing Agents / therapeutic use
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide*
  • Porphyrins / therapeutic use
  • Prospective Studies
  • Serine Endopeptidases / genetics*
  • Serpins / genetics
  • Vascular Endothelial Growth Factor A / genetics
  • Verteporfin
  • Visual Acuity / physiology

Substances

  • CFH protein, human
  • Eye Proteins
  • Nerve Growth Factors
  • Photosensitizing Agents
  • Porphyrins
  • Serpins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • pigment epithelium-derived factor
  • Verteporfin
  • Complement Factor H
  • High-Temperature Requirement A Serine Peptidase 1
  • HTRA1 protein, human
  • Serine Endopeptidases